let-7 miRNAs Can Act through Notch to Regulate Human Gliogenesis
Open accessAbstract
It is clear that neural differentiation from human pluripotent stem cells generates cells that are developmentally immature. Here, we show that the let-7 plays a functional role in the developmental decision making of human neural progenitors, controlling whether these cells make neurons or glia. Through gain- and loss-of-function studies on both tissue and pluripotent derived cells, our data show that let-7 specifically regulates decision making in this context by regulation of a key chromatin-associated protein, HMGA2. Furthermore, we provide evidence that the let-7/HMGA2 circuit acts on HES5, a NOTCH effector and well-established node that regulates fate decisions in the nervous system. These data link the let-7 circuit to NOTCH signaling and suggest that this interaction serves to regulate human developmental progression.
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This iPS-NPC line is relatively homogenous by immunostaining.
“and by immunostaining are relatively homogenous49”
From GDF10 is a signal for axonal sprouting and functional recovery after stroke (2015) · cites this paper as [49]
This iPS-NPC line is highly similar to other iPS-NPCs and ES-NPCs derived under standard conditions (Pearson correlation 0.926-0.959).
“Clustering and Pearson analysis49 demonstrate that this iPS-NPCs is highly similar to other iPS-NPCs and ES-NPCS derived under standard conditions (Pearson: 0.926–0.959)”
From GDF10 is a signal for axonal sprouting and functional recovery after stroke (2015) · cites this paper as [49]
The Cell Culture section (page unavailable) describes deriving neural progenitors from pluripotent stem-cell lines, but does not compare the citing paper’s iPS-NPC line with other iPS-NPCs or ES-NPCs. The Results section reports a Pearson comparison between let-7-treated PSC-NPCs and tissue-derived NPCs, not the claimed comparison. Searches for the 0.926–0.959 range and the iPS-NPC/ES-NPC clustering comparison found no supporting passage in our copy. (LLM, conf=0.77)
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References 44 · Cited by 103
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- Authors
- Patterson, M., Gaeta, X., Loo, K., Edwards, M., Smale, S., Cinkornpumin, J., Xie, Y., Listgarten, J., Azghadi, S., Douglass, S. M., Pellegrini, M., & Lowry, W. E.
- Affiliations
- University of California, Los Angeles (US)
- Microsoft (United States) (US)
- Corresponding author
- Lowry, W.E.
- ORCID
- Venue
- Stem Cell Reports
- Publisher
- Elsevier BV
- Published
- 2014-11
- Volume
- 3
- Issue
- 5
- Pages
- 758-773
- ISSN
- 2213-6711 (ISSN-L)
- PMC
- PMC4235151
- OpenAlex
- W2019974998
- Cited by
- 103
- References
- 44
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 5 · 2023: 5 · 2022: 5 · 2021: 12 · 2020: 10 · 2019: 11 · 2018: 11 · 2017: 15 · 2016: 11 · 2015: 7 · 2014: 1
- FWCI
- 3.94
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Stem Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Human Genome Research Institute (T32HG002536)
- National Cancer Institute (P30CA016042)
- National Institute of General Medical Sciences (P01GM099134, F31GM113641, T32GM008042, P01GM99134)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Keywords
- let-7 microRNA, Notch signaling, gliogenesis, HMGA2, Hes5, neuronal differentiation, human pluripotent stem cells, chromatin regulation
- MeSH terms
- Cell Differentiation, Cell Line, Humans, Immunohistochemistry, Nervous System, Neuroglia, Neurons, Oligodendroglia, Repressor Proteins, Signal Transduction, RNA-Binding Proteins, Gene Expression Regulation, Developmental, Reverse Transcriptase Polymerase Chain Reaction, HMGA2 Protein, RNA Interference, MicroRNAs, Pluripotent Stem Cells, Basic Helix-Loop-Helix Proteins, Basic Helix-Loop-Helix Transcription Factors, Receptors, Notch, Neurogenesis, Neural Stem Cells
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