Cited by 593Pluripotent Stem Cells ResearchNeurogenesis and neuroplasticity mechanismsNeuroscience and Neural Engineering

The DOI matches its Crossref record; 75 of the 75 references it cites were found in a registry or an index; none of the 44 sources its claims cite is checked for support yet.

Generation of Functional Human 3D Cortico-Motor Assembloids

Open access

Andersen, Jimena, Revah, Omer, Miura, Yuki, Thom, Nicholas, Amin, Neal D., Kelley, Kevin W., Singh, Mandeep, Chen, Xiaoyu, Thete, Mayuri Vijay, Walczak, Elisabeth M., Vogel, Hannes, Fan, H. Christina, Paşca, Sergiu P.·2020·Cell

DOI 10.1016/j.cell.2020.11.017PMC PMC8711252

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Abstract

SUMMARY Neurons in the cerebral cortex connect through descending pathways to hindbrain and spinal cord to activate muscle and generate movement. Although components of this pathway have been previously generated and studied in vitro, the assembly of this multi-synaptic circuit has not yet been achieved with human cells. Here, we derive organoids resembling the cerebral cortex or the hindbrain/spinal cord and assemble them with human skeletal muscle spheroids to generate 3D cortico-motor assembloids. Using rabies tracing, calcium imaging, and patch-clamp recordings, we show that corticofugal neurons project and connect with spinal spheroids, while spinal-derived motor neurons connect with muscle. Glutamate uncaging or optogenetic stimulation of cortical spheroids triggers robust contraction of 3D muscle, and assembloids are morphologically and functionally intact for up to 10 weeks post-fusion. Together, this system highlights the remarkable self-assembly capacity of 3D cultures to form functional circuits that could be used to understand development and disease.

AI snapshot

Written from the paper’s full text.

TL;DR

The paper generates three-dimensional human cortico-motor assembloids by fusing hiPS cell-derived cortical spheroids, hindbrain/cervical spinal cord spheroids, and skeletal muscle spheroids. It shows that cortical neurons connect to spinal spheroids, spinal motor neurons connect to muscle, and cortical stimulation can drive muscle contraction in vitro for up to 10 weeks.

Key findings

hSpS resembling hindbrain/cervical spinal cord were generated from hiPS cells; condition 8 (0.1 µM RA, 0.1 µM SAG, 10 ng/mL FGF-2) was selected, and DAPT exposure produced a ~3-fold increase in motor neurons and a 4-fold decrease in an undefined mixed neuronal population. Single-cell profiling included n = 7,888 cells (BD Rhapsody) and n = 9,302 cells across three hiPS cell lines (10x Genomics).
In hCS-hSpS assembloids, hCS-derived eYFP projections increased over time; rabies tracing showed ~95% of GFP+/mCherry+ hCS cells co-expressed MAP2, <4% GFAP, ~60% CTIP2, and ~12% BRN2. Optogenetic stimulation of hCS elicited calcium spikes in hSpS in 4/10 assembloids, with median response amplitude ~5 times higher than random time points (n = 16 cells, p = 0.0005), blocked by NBQX/APV; patch-clamp found reliable postsynaptic currents in 2/30 recorded Hb9+ cells across 4 assembloids.
In hSpS-hSkM assembloids, rabies tracing showed 90% of GFP+ cells were CHAT+, <5% GABA+, and ~45% ISL1+; glutamate uncaging caused muscle contraction that was blocked by curare. In hCS-hSpS-hSkM assembloids, spontaneous contractions were ~5× more frequent than hSkM alone or hCS-hSkM, and optogenetic hCS stimulation induced global contractions in 85.7% of tested assembloids and 40% of pulses, abolished by NBQX/APV.
Assembloids remained morphologically and functionally intact for up to 10 weeks; optogenetic contraction success was 50% at 8 weeks versus 81% at 5 weeks (p = 0.06), while calcium responses after 5 stimulations were more robust at 7–8 weeks (p = 0.003 for Stim 5).

Methods

Used n = 9 hiPS cell lines from 8 healthy subjects to generate human cortical spheroids (hCS), hindbrain/cervical spinal cord spheroids (hSpS), human skeletal myoblasts (hSkM), and hiPS cell-derived myoblasts (ihSkM); assembled hCS-hSpS, hSpS-hSkM, and hCS-hSpS-hSkM cultures, plus mouse E11.5 limb bud co-cultures.
Characterized cells and circuits with single-cell transcriptomics (BD Rhapsody and 10x Genomics), qPCR, immunocytochemistry, electron microscopy, rabies tracing, calcium imaging, patch-clamp electrophysiology, optogenetics, glutamate uncaging, and MUSCLEMOTION contraction analysis.
Statistical comparisons are reported throughout using p-values from the described assays; sample sizes and cell-line/differentiation details are in Table S1 and figure legends.

Limitations

The paper states that further improvements are needed: more caudal spinal cord cell types, organizing centers or other strategies to improve progenitor domain organization, assessment of ascending projections, and optimization of optogenetics with cell-type-specific reporters.
The text also notes that direct comparison to human developing hindbrain/spinal cord in the future could better address identity questions; rabies infection of 3D hSkM was challenging, yielding fewer GFP+ cells in some assembloids; and optogenetic success depends on light-pulse duration and opsin delivery efficiency.
Evident from the reported results: only 4/10 assembloids showed calcium responses in hCS-hSpS, only 2/30 recorded Hb9+ cells showed reliable postsynaptic currents, one hiPS cell line had a higher proportion of V2a neurons at the expense of motor neurons, and the hSpS single-cell analysis did not identify a clear V3 domain or non-ectodermal cells.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/j.cell.2020.11.017

Cites

75 of 75 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 44 cited sources checked · 0 supported · 0 flagged

In the paper
“RSS analysis comparing hSpS to different CNS regions in the mouse (Zeisel et al., 2018) showed that hSpS was most closely correlated to hindbrain cell types”
§ Generation of Functional Human 3D Cortico-Motor Assembloids > RESULTS > Generation of Hindbrain/Cervical Spinal Cord Spheroids from Pluripotent Stem Cells
What the sources say
- Not checked yetcites Zeisel et al., 2018 source
Load-bearingStrength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
In the paper
“We verified expression of cortico-spinal-associated markers in hCS, including FEZF2, BCL11B (CTIP2), and SOX5, using single-cell profiling of hCS (Birey et al., 2017) and found a population of cells co-expressing these genes in the glutamatergic neuron cluster but not in a subpallial-derived GABAergic cluster”
§ Generation of Functional Human 3D Cortico-Motor Assembloids > RESULTS > Generation of Cortico-Spinal Assembloids
What the sources say
- Not checked yetcites Birey et al., 2017 source
Load-bearingStrength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“We found that, overall, cluster annotation in hSpS matched previously annotated spinal cord clusters”
§ Generation of Functional Human 3D Cortico-Motor Assembloids > RESULTS > Generation of Hindbrain/Cervical Spinal Cord Spheroids from Pluripotent Stem Cells
What the sources say
- Not checked yetcites Delile et al., 2019 source
- Not checked yetcites Rosenberg et al., 2018 source
- Not checked yetcites Sathyamurthy et al., 2018 source
Load-bearingStrength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
In the paper
“we found that it broadly matched that described in the literature (Delile et al., 2019) and included glutamatergic (SLC17A6+), GABAergic (GAD1+, GAD2+ or SLC32A1+), glycinergic (SLC6A5+), and cholinergic (SLC5A7+ or SLC18A3+) cells”
§ Generation of Functional Human 3D Cortico-Motor Assembloids > RESULTS > Generation of Hindbrain/Cervical Spinal Cord Spheroids from Pluripotent Stem Cells
What the sources say
- Not checked yetcites Delile et al., 2019 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
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 observed extensive projections from the hSpS into the limb bud upon assembly”
§ Generation of Functional Human 3D Cortico-Motor Assembloids > RESULTS > Functional Assembly of Spinal Spheroids with Muscle
Load-bearingStrength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- Rests on an assumption: Mouse limb buds dissected at embryonic day 11.5 have not yet received spinal cord axonal innervation.
In the paper
“Damage or degeneration of the cortico-motor circuit following traumatic injury, amyotrophic lateral sclerosis, or autoimmune disorders result in severe motor dysfunction”
§ Generation of Functional Human 3D Cortico-Motor Assembloids > INTRODUCTION
What the sources say
- Not checked yetcites Blesch and Tuszynski, 2009
Load-bearingStrength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“We have previously developed an approach to model complex cellular interactions during human brain development by specifying region-specific spheroids or organoids and then fusing them in vitro to generate three-dimensional (3D) assembloids”
§ Generation of Functional Human 3D Cortico-Motor Assembloids > INTRODUCTION
What the sources say
- Not checked yetcites Birey et al., 2017 source
- Not checked yetcites Paşca, 2019
- Not checked yetcites Sloan et al., 2018 source
Load-bearingStrength:boosted· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“Corticofugal glutamatergic neurons in the cerebral cortex send long-range axons to modulate networks in the hindbrain and spinal cord to ultimately induce muscle contraction”
§ Generation of Functional Human 3D Cortico-Motor Assembloids > INTRODUCTION
What the sources say
- Not checked yetcites Lemon, 2008 source
- Not checked yetcites Kiehn, 2016 source
- Not checked yetcites Lodato and Arlotta, 2015 source
Load-bearingStrength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
In the paper
“This pattern of expression suggests the presence of hindbrain and spinal cord motor neuron progenitor populations in hSpS”
§ Generation of Functional Human 3D Cortico-Motor Assembloids > RESULTS > Generation of Hindbrain/Cervical Spinal Cord Spheroids from Pluripotent Stem Cells
What the sources say
- Not checked yetcites Guthrie, 2007 source
Load-bearingStrength:hedged· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“These species-specific differences are further highlighted by challenges in translating findings from animal models”
§ Generation of Functional Human 3D Cortico-Motor Assembloids > INTRODUCTION
What the sources say
- Not checked yetcites Kaiser and Feng, 2015 source
- Not checked yetcites Philips and Rothstein, 2015
- Not checked yetcites van der Worp et al., 2010 source
Load-bearingStrength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“We previously described the generation of 3D spheroids resembling the cerebral cortex (human cortical spheroids [hCS]) (Birey et al., 2017; Paşca et al., 2015; Sloan et al., 2017, 2018), which contain deep and superficial glutamatergic neurons.”
§ Generation of Functional Human 3D Cortico-Motor Assembloids > RESULTS > Generation of Cortico-Spinal Assembloids
What the sources say
- Not checked yetcites Birey et al., 2017 source
- Not matched
  Couldn’t be matched to a paper in Crossref, so it can’t be checked.
  cites Paşca et al., 2015
- Not matched
  Couldn’t be matched to a paper in Crossref, so it can’t be checked.
  cites Sloan et al., 2017, 2018
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
In the paper
“Variation in the state of hiPS cell lines can lead to divergent neuronal biases”
§ Generation of Functional Human 3D Cortico-Motor Assembloids > RESULTS > Generation of Hindbrain/Cervical Spinal Cord Spheroids from Pluripotent Stem Cells
What the sources say
- Not checked yetcites Micali et al., 2020 source
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
In the paper
“Conventional motor neuron and muscle co-cultures are not amenable to long-term experiments, as cells tend to detach over time”
§ Generation of Functional Human 3D Cortico-Motor Assembloids > RESULTS > Long-Term Culture and Functionality of Cortico-Motor Assembloids
What the sources say
- Not checked yetcites Thomson et al., 2012
Load-bearingStrength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“This represents a significant advance beyond prior models in which individual components of motor circuits have been generated in 3D in isolation or co-cultured in 2D (Duval et al., 2019; Ogura et al., 2018; Sances et al., 2016; Shi et al., 2018; Steinbeck et al., 2016).”
§ Generation of Functional Human 3D Cortico-Motor Assembloids > DISCUSSION
What the sources say
- Not checked yetcites Duval et al., 2019 source
- Not checked yetcites Ogura et al., 2018 source
- Not checked yetcites Sances et al., 2016 source
Load-bearingStrength:boosted· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes

It may state two separate claims as one. 46
The quote only partly states this claim. 2
Probably not a substantial claim. 24

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
“limb buds displayed spontaneous contractions when assembled with hSpS, but not when kept in isolation or when assembled with hCS (χ2 test, p = 0.02”
§ Generation of Functional Human 3D Cortico-Motor Assembloids > RESULTS > Functional Assembly of Spinal Spheroids with Muscle
Load-bearingStrength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
- Rests on an assumption: Mouse limb buds dissected at embryonic day 11.5 have not yet received spinal cord axonal innervation.
None of the sources cited for this claim have been checked yet.
In the paper
“Specification of the progenitor domains in the hindbrain and spinal cord relies on signaling molecules like WNT and retinoic acid (RA) secreted along the rostro-caudal axis, and sonic hedgehog (SHH) along the dorso-ventral axis”
§ Generation of Functional Human 3D Cortico-Motor Assembloids > RESULTS > Generation of Hindbrain/Cervical Spinal Cord Spheroids from Pluripotent Stem Cells
What the sources say
- Not checked yetcites Alaynick et al., 2011 source
- Not checked yetcites Goulding, 2009 source
- Not checked yetcites Jessell, 2000 source
Load-bearingStrength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“Recent evidence points at primate-specific reorganization and connectivity of the cortico-spinal pathway, including the presence of direct monosynaptic cortico-spinal connections, which may be related to corticalization of motor control and the evolution of dexterity”
§ Generation of Functional Human 3D Cortico-Motor Assembloids > INTRODUCTION
What the sources say
- Not checked yetcites Gu et al., 2017
- Not checked yetcites Lemon, 2008 source
- Not checked yetcites Sousa et al., 2017 source
Load-bearingStrength:hedged· not yet calibratedCausal:conditional· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Long-range neural projections have been observed in a cortico-thalamic assembloid (Xiang et al., 2019), in organotypic mouse co-cultures (Takuma et al., 2002) and in a preparation that used sliced cortical organoids and rodent spinal cord explants (Giandomenico et al., 2019).”
§ Generation of Functional Human 3D Cortico-Motor Assembloids > INTRODUCTION
What the sources say
- Not checked yetcites Xiang et al., 2019 source
- Not checked yetcites Takuma et al., 2002 source
- Not checked yetcites Giandomenico et al., 2019 source
Load-bearingStrength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Although components of the cortico-spinal-motor pathway have been generated or studied in isolation (Ogura et al., 2018; Sances et al., 2016; Shi et al., 2018; Steinbeck et al., 2016), the in vitro derivation and assembly of this three-part system have not yet been achieved with human cells.”
§ Generation of Functional Human 3D Cortico-Motor Assembloids > INTRODUCTION
What the sources say
- Not checked yetcites Ogura et al., 2018 source
- Not checked yetcites Sances et al., 2016 source
- Not checked yetcites Shi et al., 2018 source
Load-bearingStrength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
In the paper
“Whereas spinal cord progenitors are organized in a well-defined laminar pattern during development, post-mitotic neurons in the spinal cord do not appear to maintain this organization at later stages”
§ Generation of Functional Human 3D Cortico-Motor Assembloids > RESULTS > Generation of Hindbrain/Cervical Spinal Cord Spheroids from Pluripotent Stem Cells
What the sources say
- Not checked yetcites Lai et al., 2016 source
Strength:hedged· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“The balance between V2a interneurons and motor neurons is known to be linked (Thaler et al., 1999), and loss of motor neurons in Olig1/2 knockout mice results in a dramatic increase of Chx10+ V2a interneurons”
§ Generation of Functional Human 3D Cortico-Motor Assembloids > RESULTS > Generation of Hindbrain/Cervical Spinal Cord Spheroids from Pluripotent Stem Cells
What the sources say
- Not checked yetcites Thaler et al., 1999 source
- Not checked yetcites Zhou and Anderson, 2002
Strength:boosted· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Corticofugal projection neurons, which include cortico-spinal projecting cells, express CTIP2 and are mainly located in deep layers of the cerebral cortex, whereas neurons located in superficial layers express BRN2 and project to the contra-lateral cortex”
§ Generation of Functional Human 3D Cortico-Motor Assembloids > RESULTS > Viral Tracing, Optogenetics, and Calcium Imaging in Cortico-Spinal Assembloids
What the sources say
- Not checked yetcites Greig et al., 2013 source
Load-bearingStrength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
In the paper
“We previously showed the potential of using region-specific spheroids as a modular approach to study human interneuron migration and identify disease phenotypes (Birey et al., 2017).”
§ Generation of Functional Human 3D Cortico-Motor Assembloids > DISCUSSION
What the sources say
- Not checked yetcites Birey et al., 2017 source
Load-bearingStrength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“The hiPS cell lines used in this study were validated using standard methods as previously described (Paşca et al., 2011; Sloan et al., 2018).”
§ Generation of Functional Human 3D Cortico-Motor Assembloids > STAR★METHODS > EXPERIMENTAL MODEL AND SUBJECT DETAILS
What the sources say
- Not checked yetcites Paşca et al., 2011
- Not checked yetcites Sloan et al., 2018 source
Load-bearingStrength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
Probably not a substantial claim.

63 of 63

The paper relies on this without support.
Mouse limb buds dissected at embryonic day 11.5 have not yet received spinal cord axonal innervation.
“we dissected mouse limb buds at embryonic day 11.5 (E11.5) before spinal cord axonal innervation”

1 of 1

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Single-cell totals do not add up
Major
The two reported recovered-cell counts sum to 7,348, not 7,888. The stated total is also described as remaining after filtering, which cannot increase the count.
Reported 7888 · recomputed 7348

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Authors: Andersen, J., Revah, O., Miura, Y., Thom, N., Amin, N. D., Kelley, K. W., Singh, M., Chen, X., Thete, M. V., Walczak, E. M., Vogel, H., Fan, H. C., & Paşca, S. P.
Affiliations: Stanford Medicine (US)
BD Biosciences (United States) (US)
ORCID: Andersen, Jimena
Revah, Omer
Miura, Yuki
Thom, Nicholas
Amin, Neal D.
Kelley, Kevin W.
Singh, Mandeep
Chen, Xiaoyu
Thete, Mayuri Vijay
Vogel, Hannes
Fan, H. Christina
Venue: Cell
Publisher: Elsevier BV
Published: 2020-12
Volume: 183
Issue: 7
Pages: 1913-1929.e26
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2020.11.017
PMC: PMC8711252
OpenAlex: W3111725926
Semantic Scholar: efd4826167926999032fda07b3500f99ab4d42ee
Cited by: 593
References: 75
Citations by year: 2026: 96 · 2025: 127 · 2024: 123 · 2023: 80 · 2022: 88 · 2021: 79
FWCI: 20.02
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 387 d)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: New York Stem Cell Foundation
Chan Zuckerberg Initiative
National Institutes of Health
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neural Engineering
Keywords: spinal cord organoids, hindbrain, corticofugal neurons, motor neurons, muscle contraction, glutamate uncaging, optogenetic stimulation, calcium imaging, patch-clamp recording
MeSH terms: Animals, Calcium, Cell Differentiation, Cells, Cultured, Cerebral Cortex, Cervical Vertebrae, Gene Expression Regulation, Glutamates, Humans, Motor Cortex, Muscles, Nerve Net, Organoids, Rhombencephalon, Spinal Cord, Spheroids, Cellular, Myoblasts, Mice, Induced Pluripotent Stem Cells, Optogenetics

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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 2026-10-07, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).

A second model labelled each claim on 2026-10-07 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).

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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Generation of Functional Human 3D Cortico-Motor Assembloids

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About these checks