The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index; 22 of the 43 sources its claims cite were checked for support.
Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes
Open accessAbstract
MicroRNAs (miRNAs) have been shown to play important roles in both brain development and the regulation of adult neural cell functions. However, a systematic analysis of brain miRNA functions has been hindered by a lack of comprehensive information regarding the distribution of miRNAs in neuronal versus glial cells. To address this issue, we performed microarray analyses of miRNA expression in the four principal cell types of the CNS (neurons, astrocytes, oligodendrocytes, and microglia) using primary cultures from postnatal d 1 rat cortex. These analyses revealed that neural miRNA expression is highly cell-type specific, with 116 of the 351 miRNAs examined being differentially expressed fivefold or more across the four cell types. We also demonstrate that individual neuron-enriched or neuron-diminished RNAs had a significant impact on the specification of neuronal phenotype: overexpression of the neuron-enriched miRNAs miR-376a and miR-434 increased the differentiation of neural stem cells into neurons, whereas the opposite effect was observed for the glia-enriched miRNAs miR-223, miR-146a, miR-19, and miR-32. In addition, glia-enriched miRNAs were shown to inhibit aberrant glial expression of neuronal proteins and phenotypes, as exemplified by miR-146a, which inhibited neuroligin 1-dependent synaptogenesis. This study identifies new nervous system functions of specific miRNAs, reveals the global extent to which the brain may use differential miRNA expression to regulate neural cell-type-specific phenotypes, and provides an important data resource that defines the compartmentalization of brain miRNAs across different cell types.
Overview
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Written from the paper’s full text.
TL;DR
This study profiled miRNAs across the four principal CNS cell types and found highly cell-type-specific expression, with 116 of 351 examined miRNAs differing at least fivefold. Functional tests showed neuron-enriched miRNAs promote neuronal differentiation while glia-enriched miRNAs inhibit it and can suppress inappropriate neuronal gene expression in glia.
Key findings
- Microarray analysis of neurons, astrocytes, oligodendrocytes, and microglia from postnatal day 1 rat cortex found 116 of 351 miRNAs differentially expressed at least fivefold across the four cell types.
- Restricting to neurons, astrocytes, and oligodendrocytes, the study identified 53 neuron-enriched and 23 neuron-diminished miRNAs, 13 astrocyte-enriched and 9 astrocyte-diminished miRNAs, and 13 oligodendrocyte-enriched and 4 oligodendrocyte-diminished miRNAs.
- Overexpression of neuron-enriched miR-376a and miR-434 increased neural stem cell differentiation into neurons, whereas glia-enriched miR-223, miR-146a, miR-19, and miR-32 decreased neuronal differentiation.
- Glia-enriched miR-146a targeted neuron-specific genes including Nlgn1, Nova1, and Syt1; miR-146a inhibited neuroligin 1-dependent synaptogenesis, suggesting glial miRNAs prevent inappropriate neuronal protein expression and phenotypes.
Methods
- Primary cultures from postnatal day 1 rat cortex were used for neurons, astrocytes, oligodendrocytes, and microglia; miRNA expression was profiled on Agilent rat miRNA microarrays with three biological replicates for neurons, oligodendrocytes, and microglia and four for astrocytes.
- Differential expression was analyzed with limma using an F test across pairwise cell-type contrasts, with FDR <1%, at least fivefold change versus the average of other groups, at least twofold change versus each other group individually, and presence filters.
- Functional validation used lentiviral miRNA overexpression in rat cortical stem cells, LNA antagomirs in PC12 and C6 cells, 3′-UTR luciferase reporter assays, immunolabeling, immunoblotting, FACS of Thy1-EGFP and Gfap-EGFP mouse brain cells, and a neuroligin 1-dependent synapse formation assay.
Limitations
- The paper states that cell cultures derived from neonatal brain may still be developing and therefore may not represent mature in vivo phenotypes; it addressed this by validating selected miRNAs in acutely isolated mouse brain cells.
- The paper states that high miRNA overexpression sometimes decreased stem cell numbers, so vector concentration was reduced and data from treatments decreasing cell numbers to <35% of noninfected control were excluded.
- Evident from the text: the microarray covered 351 miRNAs, in vivo validation was limited to selected miRNAs, and for Syt1 the predicted miR-146a binding-site mutation did not abolish regulation, leaving direct versus indirect targeting unresolved.
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Claims the paper makes
41 Own result · 14 Own interpretation · 12 Partly supported · 6 Own method · 5 No full text of the sources · 4 Supported so far · 3 No basis given · 2 Couldn’t confirm · 2 Sources not found · 1 Supported · 1 Not checked yet · accuracy not yet measured
Every source the paper cites for this claim was checked and supports it.
In the paper
“These data support the hypothesis that the relative strand utilization of some miRNAs are dependent on the cell type and not purely on the thermodynamic stability of their miRNA-miRNA* hairpin duplex (Chiang et al., 2010).”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Genomic colocalization and coexpression of neural cell-typespecific miRNAs
What the sources say
- Supportedcites Chiang et al., 2010 source
In “General features of mammalian miRNAs” (page not available), the paper reports that the preferred arm switches between samples for a few miRNAs, including miR-142 in different tissues and developmental samples. Because the same miRNA hairpin shows different strand preferences across samples, these observations support the stated hypothesis that duplex thermodynamic stability alone does not determine strand utilization. (LLM, conf=0.88)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
- Supported
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In the paper
“and the astrocyte-enriched expression of miR-21, which has been reported to be under the transcriptional control of neuron-restrictive silence factor (NRSF/REST) (Jørgensen et al., 2009) and aberrantly induced in neurons after traumatic brain injury (Redell et al., 2011).”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Discussion
What the sources say
- Partly supportedcites Jørgensen et al., 2009 sourceExperimental — accuracy not yet measured
In the Results and Discussion, the paper says miR-21 had been suggested as a REST target in embryonic stem cells, but reports similar miR-21 levels in REST-deficient and wild-type cells. It therefore does not establish the attributed transcriptional control; the astrocyte-enriched expression is the citing authors’ own finding, not a claim attached to this citation. (LLM, conf=0.86)
- Not matchedcites Redell et al., 2011
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Similarly, we confirmed the glial expression of miR-219 and miR-338, which have been implicated previously in the differentiation of oligodendrocytes”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Discussion
What the sources say
- Supportedcites Lau et al., 2008 source
The Results section (‘Characterization of miRNAs expressed by oligodendrocyte lineage cells’; page unavailable) reports that miR-338 is up-regulated during oligodendrocyte differentiation and that miR-219 is strongly expressed in oligodendrocytes. This supports the attributed glial expression and the cautious description of their association with oligodendrocyte differentiation; the source does not establish that either drives differentiation. (LLM, conf=0.88)
- Not matchedcites Dugas et al., 2010
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites Zhao et al., 2010
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Neuroligin 1 is among the neuronal proteins to possess such synaptogenic activity (Scheiffele et al., 2000;Biederer and Scheiffele, 2007)”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Glia-enriched miR-146a targets neuron-specific genes and functions
What the sources say
- Supportedcites Scheiffele et al., 2000 source
The Abstract states that neuroligin-1 can trigger de novo presynaptic structure formation in vitro. The Discussion likewise reports that neuroligin-1 triggers presynaptic development in contacting CNS axons, supporting the attributed synaptogenic activity. (LLM, conf=0.95)
- Not checked — no full text of the sourcecites Biederer and Scheiffele, 2007 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“the negative regulation of which has also been found to promote neuronal differentiation in other studies (Ohtsuka et al., 1999; Fig. 7 I, K ).”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Genomic colocalization and coexpression of neural cell-typespecific miRNAs
What the sources say
- Partly supportedcites Ohtsuka et al., 1999 sourceExperimental — accuracy not yet measured
The indexed Abstract reports that activated Notch inhibited neuronal differentiation in Hes5-null cells, but not in cells lacking both Hes1 and Hes5. This supports a role for Hes5 alongside Hes1, not the claim that negative regulation of Hes5 alone promotes neuronal differentiation. (LLM, conf=0.85)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These results show that several miRNAs had strong effects on neural stem cell differentiation.”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Genomic colocalization and coexpression of neural cell-typespecific miRNAs
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Interestingly, however, there were three miRNA-miRNA* pairs that were found to have opposite expression patterns (i.e., they maintained a different strand in microglia compared with the other three cell types).These pairs are as follows: miR-125-5p/ miR-125-3p, miR-138/miR-138*, and miR-99b/miR-99b* (Fig. 5).”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Genomic colocalization and coexpression of neural cell-typespecific miRNAs
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“overexpression of the neuron-enriched miRNAs miR-376a and miR-434 increased the differentiation of neural stem cells into neurons”
- Also stated in: § Genomic colocalization and coexpression of neural cell-typespecific miRNAs · plain
“Of our newly identified neuron-enriched miRNAs, miR-376a and miR-434 also increased the number of cells differentiating toward a neuronal phenotype, with an effect size similar to miR-124 (Fig. 6C).”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: miRNAs bind to mRNAs by sequence complementarity and direct their degradation or translational repression.
- Also stated in: § Genomic colocalization and coexpression of neural cell-typespecific miRNAs · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These studies confirmed the neuron-enriched expression of miR-376a and miR-434 and the neuron-diminished expression of miR-223, miR-146a, and miR-19a (Fig. 3B).”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Individual neural cell types have distinct miRNA expression profiles
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“whereas the opposite effect was observed for the glia-enriched miRNAs miR-223, miR-146a, miR-19, and miR-32.”
- Also stated in: § Genomic colocalization and coexpression of neural cell-typespecific miRNAs · plain
“Several glia-enriched miRNAs decreased the number of stem cells differentiating into neurons, which was apparent by a decreased fraction of Tuj1 ϩ cells (Fig. 6C).”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: miRNAs bind to mRNAs by sequence complementarity and direct their degradation or translational repression.
- Also stated in: § Genomic colocalization and coexpression of neural cell-typespecific miRNAs · plain
- It may state two separate claims as one. 20
- Probably not a substantial claim. 20
- The quote only partly states this claim. 1
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“MicroRNAs (miRNAs) have been shown to play important roles in both brain development and the regulation of adult neural cell functions.”
- Also stated in: § Introduction · plain
“Recent studies have shown that numerous miRNAs exist in mammalian systems, where they play important roles in development, are responsible for regulating cell-type-specific functions in the adult organism, and are involved in disease processes (Bartel, 2009).”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Abstract
What the sources say
- Partly supportedcites Bartel, 2009 sourceExperimental — accuracy not yet measured
In “Roles of specific miRNA:target interactions” (page not provided), the review says miRNA regulation is needed for development of the Drosophila peripheral nervous system, but does not establish a role in brain development specifically. “Binary switches and much more” describes miR-8 regulation that prevents neurodegeneration, but does not identify this as regulation of adult neural cell functions. (LLM, conf=0.84)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § Introduction · plain
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Previous studies had instead compared the miRNA expression in whole brain tissue with the expression in other tissues of the same organism (Sempere et al., 2004;Wienholds et al., 2005) or assessed differences in miRNA expression during different stages of development of individual neural cell types (Krichevsky et al., 2003;Smirnova et al., 2005;Zhao et al., 2010).”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Individual neural cell types have distinct miRNA expression profiles
What the sources say
- Supportedcites Sempere et al., 2004 source
The Results and discussion section (“Diverse miRNA expression patterns in mammalian organs”) reports profiling miRNA expression across adult mouse and human organs, including brain, and identifies brain-specific and brain-enriched miRNAs relative to other organs. It also says future work would determine which neuronal cells express them, consistent with this citation supporting the whole-organ comparison rather than the separate neural-cell-development clause. (LLM, conf=0.93)
- Not checked — no full text of the sourcecites Wienholds et al., 2005 source
- Partly supportedcites Krichevsky et al., 2003 sourceExperimental — accuracy not yet measured
The ‘miRNA expression during corticogenesis’ section reports comparing miRNA expression across developmental stages, using RNA from rat forebrains. It does not establish that those developmental comparisons were made in individual neural cell types; the cultured-neuron work described in the paper concerns a different analysis. (LLM, conf=0.88)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The largest miRNA cluster discovered to date consists of Ͼ50 miRNAs in the human imprinted 14q32 domain (Seitz et al., 2004), which has orthologous clusters in the rat (6q32) and mouse (12qF1).”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Genomic colocalization and coexpression of neural cell-typespecific miRNAs
What the sources say
- Partly supportedcites Seitz et al., 2004 sourceExperimental — accuracy not yet measured
The paper’s Identification of miRNA Genes at Human 14q32 Domain section describes the human 14q32 cluster as the largest reported to date, but counts 40 genes in the cluster—not more than 50. The paper also reports a homologous cluster in the mouse distal 12 region; it does not establish the stated rat 6q32 location. (LLM, conf=0.90)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“As a positive control, we showed that neuronal miR-124 increased the differentiation of stem cells toward neuronal cell fate, in agreement with previous observations (Krichevsky et al., 2003).”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Genomic colocalization and coexpression of neural cell-typespecific miRNAs
What the sources say
- Partly supportedcites Krichevsky et al., 2003 sourceExperimental — accuracy not yet measured
The ‘miRNA expression during corticogenesis’ section reports that miR-124a expression rose during embryonic brain development. It does not report that miR-124 increased stem-cell differentiation toward a neuronal fate; the ‘miRNA expression in Presenilin-1 knockout mice’ section discusses a possible role for miRNAs in lineage decisions, not a demonstrated effect of miR-124. (LLM, conf=0.82)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Interestingly, a few miRNAs within this cluster have been implicated in regulating synapse-specific genes (Schratt et al., 2006) and shown to exhibit neuronal-activitydependent expression (Fiore et al., 2009).”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Genomic colocalization and coexpression of neural cell-typespecific miRNAs
What the sources say
- Not checked — no full text of the sourcecites Schratt et al., 2006 source
- Supportedcites Fiore et al., 2009 source
The Fiore et al. citation is attached to the neuronal-activity-dependent expression claim, not the preceding claim about synapse-specific genes. In Results, “The miR379–410 cluster is co-regulated by neuronal activity” (page not provided), the paper reports increased expression of tested cluster miRNAs after neuronal depolarization. (LLM, conf=0.93)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Studies investigating the relative thermodynamic stability of the two ends of the pre-miRNA duplex indicated that the strand in which the 5Ј end is less tightly paired to its complement remains associated with Ago and performs the functions of the mature miRNA (Khvorova et al., 2003;Schwarz et al., 2003).”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Genomic colocalization and coexpression of neural cell-typespecific miRNAs
What the sources say
- Supportedcites Khvorova et al., 2003 source
The Results and Discussion (page unavailable) state that, in the miRNAs and siRNAs examined, the strand with lower internal stability at its 5′ end is retained within RISC. The paper links this strand selection to RNA-interference function, supporting the citing sentence’s paraphrase. (LLM, conf=0.91)
- Partly supportedcites Schwarz et al., 2003 sourceExperimental — accuracy not yet measured
The Introduction says the strand with the less tightly paired 5′ end is selected for RISC loading and proposes that the miRNA strand enters RISC while the other is degraded. This supports the strand-selection mechanism, but the paper presents its extension to miRNAs as a proposal and does not establish the claim specifically as continued association with Ago. (LLM, conf=0.86)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“The physiological importance of miRNAs in nervous system functions and disease states has also been suggested by previous studies of a small number of brainenriched miRNAs (Leucht et al., 2008;Mellios et al., 2008;Packer et al., 2008;Cheng et al., 2009;Schratt, 2009).”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Introduction
What the sources say
- Not checked — no full text of the sourcecites Leucht et al., 2008 source
- Supportedcites Mellios et al., 2008 source
The Introduction states that miRNAs have roles in nervous-system development and synaptic plasticity and that brain-expressed miRNAs have been implicated in brain diseases. The Discussion adds that this study’s findings support a role for developmentally regulated miRNAs in modulating BDNF expression in human prefrontal cortex, while treating their significance in psychiatric disease as a possibility requiring further study. That supports the citing sentence’s qualified wording, “suggested.” (LLM, conf=0.90)
- Supportedcites Packer et al., 2008 source
The Introduction describes miRNAs as modulators of cell fate and function, while the Discussion describes roles for brain-enriched miR-9 in neural development. The Results report reduced levels of several miRNAs, including miR-9, with Huntington’s disease progression. This study therefore supports the citing sentence’s suggested importance of brain-enriched miRNAs in nervous-system function and disease. (LLM, conf=0.92)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“miRNAs are frequently found in genomic clusters (Bartel, 2009).”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Genomic colocalization and coexpression of neural cell-typespecific miRNAs
What the sources say
- Could not verifycites Bartel, 2009 sourceExperimental — accuracy not yet measured
The section “The miRNAs” discusses the number of identified miRNA genes but not whether they occur in genomic clusters. Searches for “genomic clusters” and clustered or polycistronic miRNA loci found no passage in our copy addressing how frequently miRNAs are clustered. (LLM, conf=0.70)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Compared with other organs, the brain has a particularly high percentage of tissue-specific and tissue-enriched miR-NAs (Lagos-Quintana et al., 2002;Kim et al., 2004;Sempere et al., 2004;Smirnova et al., 2005).”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Introduction
What the sources say
- Not matchedcites Lagos-Quintana et al., 2002
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites Kim et al., 2004
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Supportedcites Sempere et al., 2004 source
The Conclusions (page not provided) state that 13 of 17 miRNAs identified as organ-specific or organ-enriched in both mouse and human were associated with the brain. The Results and discussion section also lists more brain-specific and brain-enriched miRNAs than for any other individual organ examined. (LLM, conf=0.94)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Neural tissue is highly heterogeneous, being composed of different types of neurons, astrocytes, and oligodendrocytes, which de-velop from a common pool of neural progenitor cells (Gage, 2000), and microglia, which develop from the hematopoietic lineage (Ritter et al., 2006).”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Introduction
What the sources say
- Not checked — no full text of the sourcecites Gage, 2000 source
- Supportedcites Ritter et al., 2006 source
The citation is attached to the microglia clause, not the claims about neurons, astrocytes, or oligodendrocytes. In “Transplanted CD44 hi cells differentiate into microglia” (page unavailable), the paper reports that bone-marrow myeloid progenitors differentiate into microglia and calls microglia the retina’s resident myeloid population, supporting the attributed lineage distinction. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The small RNA cloning strategy used to identify mature miRNAs revealed that the process of the strand selection by Ago is not symmetrical (Lim et al., 2003).”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Genomic colocalization and coexpression of neural cell-typespecific miRNAs
What the sources say
- Partly supportedcites Lim et al., 2003 sourceExperimental — accuracy not yet measured
In “Molecular abundance of miRNAs” (page unavailable), the paper reports that RNA from one hairpin arm was cloned much more frequently than RNA from the other. In “miRNA biogenesis” (page unavailable), it offers preferential entry into the miRNP/RISC complex as a possible explanation, not an established mechanism. The cloning results support asymmetric accumulation, but do not establish that Ago performs the asymmetric strand selection. (LLM, conf=0.87)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“which have been reported to stimulate neuronal differentiation (Fode et al., 2000;Li et al., 2008; Fig. 7 F, H, J, L).”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Genomic colocalization and coexpression of neural cell-typespecific miRNAs
What the sources say
- Partly supportedcites Fode et al., 2000 sourceExperimental — accuracy not yet measured
The section “Ngn2 functions as a neuronal determination gene in cortical lineages” says Ngn1 helps induce overt neuronal differentiation in subsets of sensory cranial ganglia, supporting the Neurog1 part of the claim. Our copy does not address Mef2c, so it does not support the claim about both genes. (LLM, conf=0.86)
- Not matchedcites Li et al., 2008
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“While confirming that miR-124 is a potent determinant of neuronal identity (Krichevsky et al., 2003;Visvanathan et al., 2007)”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Discussion
What the sources say
- Partly supportedcites Krichevsky et al., 2003 sourceExperimental — accuracy not yet measured
The ‘miRNA expression during corticogenesis’ section reports that miR-124a expression rose more than 13-fold during embryonic brain development. That supports an association with development, but not the claim that miR-124 determines neuronal identity; the Introduction says that no mammalian miRNA function had yet been demonstrated. Page numbers are unavailable in our copy. (LLM, conf=0.88)
- Not matchedcites Visvanathan et al., 2007
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“the targeting of which has been shown previously to mediate miR-124-dependent proneuronal differentiation of neural stem cells (Krichevsky et al., 2003;Fig. 7 E, G).”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Genomic colocalization and coexpression of neural cell-typespecific miRNAs
What the sources say
- Could not verifycites Krichevsky et al., 2003 sourceExperimental — accuracy not yet measured
The miRNA expression during corticogenesis section reports increased miR-124a expression during brain development, but does not establish a role in neural stem-cell differentiation. The putative mRNA targets section discusses other miRNAs and targets; searches for Stat3 and miR-124-dependent differentiation found no passage showing that Stat3 targeting mediates the claimed effect. Page numbers were unavailable in our copy. (LLM, conf=0.74)
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Could not verify
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This analysis yielded multiple enriched or diminished miRNAs for neurons and microglia and relatively fewer miRNAs detected as uniquely enriched or diminished in astrocytes or oligodendrocytes (Table 1).”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Individual neural cell types have distinct miRNA expression profiles
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These analyses revealed that neural miRNA expression is highly cell-type specific, with 116 of the 351 miRNAs examined being differentially expressed fivefold or more across the four cell types.”
- Also stated in: § Individual neural cell types have distinct miRNA expression profiles · plain
“These analyses showed that neural cell types have remarkably distinct miRNA expression profiles (Fig. 2), with 116 of the examined 351 miRNAs being at least fivefold differentially expressed across the four cell types.”
- Also stated in: § Introduction · plain
“Consistent with our hypothesis, our analyses showed that neural cell subtypes differed extensively in their miRNA expression patterns.”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § Individual neural cell types have distinct miRNA expression profiles · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Among the miRNAs exhibiting cell-type-specific expression among the four cell types, only 3 clusters were detected: a microglia-enriched cluster on Chr4q42 comprising miR-141 and miR-200c and two neuron-enriched clusters on Chr6q32”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Genomic colocalization and coexpression of neural cell-typespecific miRNAs
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we identified 53 enriched and 23 diminished miRNAs in neurons, 13 enriched and 9 diminished miRNAs in astrocytes, and 13 enriched and 4 diminished miRNAs in oligodendrocytes (Table 2).”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Individual neural cell types have distinct miRNA expression profiles
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“By implementing the same approach using Gfap-EGFP transgenic mice, we likewise confirmed the astrocyte-enriched expression of miR-143, miR-193, and miR-449a and the astrocyte-diminished expression of miR-327 and miR-494 (Fig. 3C,D).”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Individual neural cell types have distinct miRNA expression profiles
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Of 43 duplex pairs we identified among our differentially expressed miRNAs, 39 showed correlated expression in which one of the two strands was always present at higher levels”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Genomic colocalization and coexpression of neural cell-typespecific miRNAs
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one. The quote only partly states this claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Comparing differential miRNA expression only across neurons, astrocytes, and oligodendrocytes, four additional clusters were found: two neuron-diminished clusters on Chr15q24 comprisingmiR-17-3p,miR-17-5p,miR-18a,miR-19a,miR-20a,miR-20a*, and miR-92a and on ChrXq36 comprising miR-322, miR-322*, miR-351, miR-450a, miR-503, miR-542-3p, miR-542-5p, and two astrocyte-enriched clusters on ChrXq12”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Genomic colocalization and coexpression of neural cell-typespecific miRNAs
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Moreover, hierarchical clustering of the expression profiles showed that cell types of common developmental origin differed least in their miRNA composition (astrocytes and oligodendrocytes), while neurons and microglia showed more unique miRNA expression profiles.”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Discussion
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Therefore, we decreased the concentration of the applied vector to limit overexpression levels of each miRNA to a maximum of 100-fold compared with endogenous.”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Genomic colocalization and coexpression of neural cell-typespecific miRNAs
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“However, the full scope of miRNA-mediated regulation of brain functions is largely unknown.”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Introduction
plain- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“By using FACS on brain samples of mice expressing EGFP under the control of the Thy1 promoter, we were able to successfully separate neurons from glial cells as confirmed by enrichment of neuronal marker Tubb3 and neuronal miR-124 in Thy1 ϩ cells compared with Thy1 Ϫ cells (Fig. 3A).”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Individual neural cell types have distinct miRNA expression profiles
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“As we have shown in recent cell-resolved analyses of brain tissue, brain parenchyma is principally composed of the 4 neural cell types (neurons, astrocytes, oligodendrocytes, and microglia), with insignificant contributions from endothelial cells, pericytes, fibroblasts, smooth muscle cells, and erythrocytes (Kuhn et al., 2011).”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > RNA isolation and qPCR analysis.
What the sources say
- Not checked — no full text of the sourcecites Kuhn et al., 2011 source
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition, we did not take into consideration any data from treatments that decreased the numbers of cells to Ͻ35% of the noninfected control.”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Genomic colocalization and coexpression of neural cell-typespecific miRNAs
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Interestingly, miRNAs show varying levels in different organs, which is consistent with their anticipated role in regulating tissue-specific protein expression (Lagos-Quintana et al., 2002).”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Introduction
What the sources say
- Not matchedcites Lagos-Quintana et al., 2002
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“The cellular composition of these cultures was verified by immunocytochemistry using antibodies against well established cell-type-specific marker antigens: NeuN/Rbfox (neuronal nuclear antigen/RNA binding protein Fox) for mature neurons, GFAP (glial fibrillary acidic protein) for astrocytes, O4 antigen for oligodendrocytes, and integrin ␣ M chain (Itgam) for microglia (Kuhn et al., 2011).”
- Also stated in: § Individual neural cell types have distinct miRNA expression profiles · hedged
“These mRNA expression values indicated largely segregated expression of the cell-type-specific RNAs, further confirming that the primary cultures used for expression analyses represented the intended cell populations (Fig. 1).”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Individual neural cell types have distinct miRNA expression profiles
What the sources say
- Not checked — no full text of the sourcecites Kuhn et al., 2011 source
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § Individual neural cell types have distinct miRNA expression profiles · hedged
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“MicroRNAs (miRNAs) are 19-to 24-nucleotide (nt) noncoding RNAs that act as important regulators of posttranscriptional gene expression (Ambros, 2004;Kim, 2005).”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Introduction
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“By extension, this also implies that the targeting of other neuronal mRNAs by miR-146a and other glia-enriched miRNAs might likewise prevent glia from mistakenly adopting neuron-specific phenotypes.”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Glia-enriched miR-146a targets neuron-specific genes and functions
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“It has been shown previously that heterologous expression of key synaptogenic proteins in non-neuronal cells allows them to receive projections from neurons and subsequently induce morphological and functional presynaptic differentiation in the contacting axons (Biederer and Scheiffele, 2007).”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Glia-enriched miR-146a targets neuron-specific genes and functions
What the sources say
- Not checked — no full text of the sourcecites Biederer and Scheiffele, 2007 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These studies therefore provide novel evidence that cell-type-specific miRNAs have important roles in both establishing and maintaining distinct neuronal and glial phenotypes.”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Discussion
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“this result implies that Syt1 is a target of miR-146a, but that the actual binding site is different from the predicted one”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Glia-enriched miR-146a targets neuron-specific genes and functions
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
miRNAs bind to mRNAs by sequence complementarity and direct their degradation or translational repression.
“miRNAs bind to messenger RNAs (mRNAs) based on sequence complementarity and direct the degradation or repression of translation of the mRNAs to which they are bound (known as their targets).”
The paper relies on this without support.
The heterogeneous phenotypes of neural cells must be established during cell specification and maintained throughout the life of the adult organism.
“The heterogeneous phenotypes of the various neural cells must be established during cell specification and be maintained throughout the life of the adult organism.”
The paper relies on this without support.
A genome-wide investigation of miRNA expression in neurons, astrocytes, oligodendrocytes, and microglia had not been available previously.
“However, a genome-wide investigation of miRNA expression in neurons, astrocytes, oligodendrocytes, and microglia had not been available previously.”
The paper relies on this without support.
Sequence-based target prediction alone is subject to false-positive identification.
“Because sequence-based target prediction alone is subject to false-positive identification”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“A previous study reported that miR-146a-5p is a microglia-enriched miRNA, not present in hippocampal neurons, and expressed at much lower extent in astrocytes.29”
From Microglia secrete miR-146a-5p-containing exosomes to regulate neurogenesis in depression (2022) · cites this paper as [29]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“MiR-146a-5p targets the postsynaptic cell-adhesion molecule neuroligin1 (Nlg1), the dendritic protein MAP1A and the synaptic vesicle protein synaptotagmin1 (Syt1) [39];”
From Glia-to-neuron transfer of miRNAs via extracellular vesicles: a new mechanism underlying inflammation-induced synaptic alterations (2018) · cites this paper as [39]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Among the three miRNAs upregulated in EVs produced by inflammatory microglia, miR-146a-5p is a microglia-enriched miRNA, detectable at lesser extend in astrocytes, and it prevents the expression of neuronal genes in neuron progenitors [39].”
From Glia-to-neuron transfer of miRNAs via extracellular vesicles: a new mechanism underlying inflammation-induced synaptic alterations (2018) · cites this paper as [39]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In HD, the dysregulation of miRNAs has been reported in HD in vitro models, transgenic HD animals and human HD brain [12-24].”
From miR-10b-5p expression in Huntington’s disease brain relates to age of onset and the extent of striatal involvement (2015) · cites this paper as [16]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The brain expresses the greatest diversity of miRNAs, with several unique to the brain and to specific brain cell types (Bak et al., 2008; Jovicic et al., 2013; Nowakowski et al., 2018).”
From Brain cell-specific origin of circulating microRNA biomarkers in experimental temporal lobe epilepsy (2023) · cites this paper as Jovicic et al., 2013
Experimental — accuracy not yet measured
The cited source says what the claim attributes to it.
In the citing paper
“It has been reported that glial-enriched miR-146a-5p can inhibit neuronal differentiation.29”
From Microglia secrete miR-146a-5p-containing exosomes to regulate neurogenesis in depression (2022) · cites this paper as [29]
The cited source says what the claim attributes to it.
In the citing paper
“Additionally, miRs often display cell type–specific regulation of their targets. 62 , 63”
From Deletion of miR-33, a regulator of the ABCA1–APOE pathway, ameliorates neuropathological phenotypes in APP/PS1 mice (2024) · cites this paper as [62]
The cited source says what the claim attributes to it.
In the citing paper
“This identified a set of miRNAs that are enriched in neurons, with expression fivefold higher than the glial cells, including miR-124, miR-132 and miR-135b, while the same cells display very low expression of miR-21 and miR-146a compared to glial cells [8].”
From Shared and distinct microRNA profiles between HT22, N2A and SH-SY5Y cell lines and primary mouse hippocampal neurons (2025) · cites this paper as [8]
The cited source says what the claim attributes to it.
In the citing paper
“miRNAs enriched in microglial cultures (miR-126-5p, miR-126-3p, miR-141, miR-142-3p, miR-142-5p, miR-150, miR-200c and miR-223) were all were up-regulated.”
From miR-10b-5p expression in Huntington’s disease brain relates to age of onset and the extent of striatal involvement (2015) · cites this paper as [16]
The cited source says what the claim attributes to it.
In the citing paper
“Additional advantages of miRNAs over other biomarkers, such as proteins, is that they are stable in bodily fluids, 9 many have restricted expression in the tissues they regulate, 10 and they are accurately quantified by routine and fast laboratory methods (such as RT‐qPCR) that are available in most clinical laboratories.”
From Validation of differentially expressed brain‐enriched microRNAs in the plasma of PD patients (2020) · cites this paper as [10]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“miR-135a expressed in mouse hippocampal neurons was reported to be essential for the regulation of excitatory neurotransmission [54, 55].”
From Differential RNA packaging into small extracellular vesicles by neurons and astrocytes (2021) · cites this paper as [54]
Experimental — accuracy not yet measuredIn the citing paper
“Previous microarray data (41) and data obtained from cell cultures (42) also pointed to an enriched expression of miR-146a in microglia compared to other CNS resident cells.”
From Absence of miRNA-146a Differentially Alters Microglia Function and Proteome (2020) · cites this paper as [41]
In the citing paper
“miR-23 is involved in neuronal specification, and miR-146a implicated in the prevention of neuroligin 1-dependent synaptogenesis, and both were enriched in astrocytes compared to neurons [54, 67].”
From Differential RNA packaging into small extracellular vesicles by neurons and astrocytes (2021) · cites this paper as [54]
In the citing paper
“miRNAs found to be specifically enriched in neuronal cultures (miR-129-3p, miR-129-5p, miR-132, miR-135b, miR-431, miR-433) were all down-regulated in our study”
From miR-10b-5p expression in Huntington’s disease brain relates to age of onset and the extent of striatal involvement (2015) · cites this paper as [16]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Genomic colocalization and coexpression of neural cell-typespecific miRNAs
“neuronenriched miRNAs comprised miR-124, miR-367a, and miR-434”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Genomic colocalization and coexpression of neural cell-typespecific miRNAs
“Of our newly identified neuron-enriched miRNAs, miR-376a and miR-434 also increased the number of cells differentiating toward a neuronal phenotype”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Discussion
“B, Glia-like cell line C6 shows enriched expression of neuronal miRNAs compared with glia-like C6 cells.”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Discussion
“**p Ͻ 0.01 by unpaired t test comparing C6 and PC12 RNA samples.”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Discussion
“The neuron-diminished cluster on Chr15q24 comprises rno-miR-17-3p, miR-17-5p, miR-18a, miR-19a, miR-20a, miR-20a, and miR-92a.”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Genomic colocalization and coexpression of neural cell-typespecific miRNAs
“on Chr15q24 comprisingmiR-17-3p,miR-17-5p,miR-18a,miR-19a,miR-20a,miR-20a*, and miR-92a”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Genomic colocalization and coexpression of neural cell-typespecific miRNAs
“two astrocyte-enriched clusters on ChrXq12 comprising miR-34b and miR-34c and on Chr8q24 comprising miR-221 and miR-222”
§ Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes > Discussion
“The astrocyte-enriched cluster on Chr8q24 comprises rno-miR-34b and miR-34c.”
Citations
Cites
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nature Protocols · doi:10.1038/nprot.2008.211 · Cited by 35,890
MicroRNAs: Target Recognition and Regulatory Functions
Bartel, D. P. (2009) · Cell · doi:10.1016/j.cell.2009.01.002 · Cited by 20,068
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Metadata
- Authors
- Jovičić, A., Roshan, R., Moisoi, N., Pradervand, S., Moser, R., Pillai, B., & Luthi-Carter, R.
- Affiliations
- École Polytechnique Fédérale de Lausanne (CH)
- Institute of Genomics and Integrative Biology (IN)
- University of Leicester (GB)
- University of Lausanne (CH)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2013-03-20
- Volume
- 33
- Issue
- 12
- Pages
- 5127-5137
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6705001
- OpenAlex
- W2020613231
- Cited by
- 251
- References
- 53
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 13 · 2023: 18 · 2022: 13 · 2021: 29 · 2020: 24 · 2019: 24 · 2018: 20 · 2017: 23 · 2016: 22 · 2015: 20 · 2014: 18 · 2013: 12
- FWCI
- 8.43
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- SERVAL (Université de Lausanne) (publishedVersion, other-oa)
- IRIS (submittedVersion)
- Funders
- Council of Scientific and Industrial Research, India (BSC 0123)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- microRNA, miR-146a, miR-376a, miR-223, neural stem cell differentiation, astrocytes, oligodendrocytes, microglia, neuroligin-1, synaptogenesis, glial reprogramming
- MeSH terms
- Animals, Animals, Newborn, Astrocytes, Cell Differentiation, Cerebral Cortex, Female, Male, Neuroglia, Neurons, Oligodendroglia, Phenotype, Synapses, Microglia, MicroRNAs, Rats, Neural Stem Cells, Transcriptome, Primary Cell Culture
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-11-06, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-11-06 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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