Evidence map›Paper›PMID 42660945›Full record

ArticleNature communications2026

Distinct differentiation trajectories leave lasting impacts on gene regulation and function of V2a neurons.

Nicholas H Elder, Alireza Majd, Andrius Cesiulis, Spencer Nyarady, Kalyan Sankar, Emily A Bulger, Ryan M Samuel, Lyandysha V Zholudeva, Todd C McDevitt, Faranak Fattahi

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Nicholas H ElderDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA.
Alireza MajdDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0003-0036-2725
Andrius CesiulisDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA.
Spencer NyaradyDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA.
Kalyan SankarDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA.
Emily A BulgerDevelopmental and Stem Cell Biology Graduate Program, University of California, San Francisco, CA, USA.ORCID 0000-0003-2967-1994
Ryan M SamuelDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA.
Lyandysha V ZholudevaGladstone Institute of Cardiovascular Disease, Gladstone Institutes, San Francisco, CA, USA.
Todd C McDevittGladstone Institute of Cardiovascular Disease, Gladstone Institutes, San Francisco, CA, USA.
Faranak FattahiDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA. Faranak.Fattahi@ucsf.edu.ORCID 0000-0002-9473-8596

Funding

Understanding Hirschsprung disease using hPSC-derived models of the enteric nervous systemR01DK142437 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FATTAHI, FARANAK · 2025 to 2025
$2.8M
Illumina NovaSeq 6000 Sequencing SystemS10OD028511 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHOW, ERIC D · 2020 to 2020
$583k
California Institute for Regenerative Medicine (CIRM) DISC0-14521California Institute for Regenerative Medicine (CIRM) DISC2-15119California Institute for Regenerative Medicine (CIRM) DISC2-16715NIDDK NIH HHS R01 DK142437NIH HHS S10 OD028511U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) R01DK142437
6 · The paper itself

Abstract

V2a interneurons are excitatory neurons found throughout the hindbrain and spinal cord, two regions that arise from distinct progenitors during embryonic development. Whether this lineage difference shapes mature gene regulation and function is unknown. V2a neurons show plasticity after spinal cord injury and are candidates for cell therapy. We differentiated human stem cells into V2a neurons through hindbrain- and spinal cord-like progenitor routes and profiled them by single nucleus multiomic sequencing. The two lineages showed distinct transcription factor motif enrichment and differentially expressed genes governing axon growth and calcium handling. Inducing V2a transcription factors directly, bypassing developmental patterning, produced a population unlike either lineage, confirming progenitor history is not interchangeable. Using CellOracle and lentiviral knockdown, we identified CREB5 and TCF7L2 as regulators specific to the spinal-like lineage. These results show that progenitor origin shapes V2a identity and reveal new regulators of neural diversity along the anterior-posterior axis.

Indexed as

Cell DifferentiationInterneuronsNeuronsAnimalsCell LineageGene Expression Regulation, DevelopmentalHumansNeural Stem CellsRhombencephalonSpinal CordTranscription Factor 7-Like 2 ProteinTranscription FactorsTranscription Factor 7-Like 2 ProteinTranscription Factors

Identifiers

PMID42660945
PMCPMC13522347

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.