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Nrsn1-Smarcc1 Coupling Regulates Neural Stem Cell Differentiation and Chronic-phase Recovery After Ischemic Stroke.

Overview

Authors: Ruolin Zhang1,2, Chang Liu3,4,5, Yuneng Zhou1, Kaichen Zhao1, Muyang Li1, Bingcheng Cai1, Ying Wang1, Zhiyuan Yuan1,6, Zhaoxin Liu1, Zilong Yuan7, Yao Xiao1,6, Peiyang Zhou6, Ke Shui1, Wendai Bao1, Min Zhang1, Jun Qin2, Jun Chen2, Xin Yang1,8, Zhiqiang Dong1,2,6,7,9
ORCID iDs: Ruolin Zhang, Muyang Li, Bingcheng Cai, Min Zhang, Xin Yang, Zhiqiang Dong
  1. College of Biomedicine and Health, College of Life science and Technology, Huazhong Agricultural University, Wuhan, China
  2. Hubei Provincial Clinical Research Center for Central Nervous System Repair and Functional Reconstruction, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China
  3. State Key Laboratory of Genome and Multi‐omics Technologies, BGI Research, Shenzhen, China
  4. Shanxi Medical University‐BGI Collaborative Center For Future Medicine, Shanxi Medical University, Taiyuan, China
  5. Shenzhen Key Laboratory of Single‐Cell Omics, BGI Research, Shenzhen, China
  6. Department of Neurology, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei, China
  7. Hubei Cancer Hospital, Tongji Medical College, Wuhan, Hubei, China
  8. Department of Electrical and Electronic Engineering, School of Engineering, Cardiff University, Cardiff, UK
  9. Hubei Jiangxia Laboratory, Wuhan, Hubei, China
Institutions: Hubei University of Medicine (China); Huazhong Agricultural University (China); Taihe Hospital (China); BGI Group (China) (China); Shanxi Medical University (China); BGI Research (China); Hubei Cancer Hospital (China); Xiang Yang No.1 People's Hospital (China); Cardiff University (United Kingdom)
Journal: Advanced science (Weinheim, Baden-Wurttemberg, Germany), article e77547
Dates: received 15 March 2026; accepted 24 August 2026; published online 3 September 2026; in print September 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1002/advs.77547 · PMID 42693582 · PMCID PMC13542395 · OpenAlex W7208775979
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: mouse (organism), stroke (population), developmental (subfield)
Methods: Preprocessing, Statistics, Smoothing, state filtering, decompositions, Evoked potentials, Connectivity, Machine learning, fMRI & imaging
Keywords: Foxa2, Ischemia‐reperfusion, Neuronal differentiation, Nrsn1, NSC, Smarcc1
Topic: Neurogenesis and neuroplasticity mechanisms (Developmental Neuroscience, Neuroscience), according to OpenAlex
Funding: Hubei Provincial Natural Science Foundation (2025AFD036); Shenzhen Key Laboratory of Single-Cell Omics (SYSPG20260518092302004); Natural Science Foundation of Hubei Province (2025AFD036); Hangzhou Science and Technology Department (2024SZD1B09); National Natural Science Foundation of China (32400815, 32571174)
Citations: not cited yet (Europe PMC); 78 references in the paper

Abstract

Stroke remains a leading cause of long‐term neurological disability worldwide, largely due to irreversible neuronal loss and the limited regenerative capacity of the adult mammalian brain. Neural stem cells (NSCs) in the adult brain possess the potential to generate new neurons after injury, yet the molecular mechanisms regulating their neuronal differentiation following ischemic insult remain incompletely understood. Here, integrating single‐cell multi‐omics analyses with spatial transcriptomics, we systematically delineated cell type‐specific spatiotemporal dynamics in the striatum of a mouse model of ischemia‐reperfusion injury. We identified Neurensin 1 (Nrsn1) as a gene markedly upregulated during NSC‐derived neuronal differentiation in the recovery phase. Mechanistically, Foxa2 directly activates Nrsn1 transcription, whereas Nrsn1 promotes neuronal differentiation by facilitating the nuclear translocation of the chromatin‐remodeling factor Smarcc1 in vitro. In vivo, both endogenous NSCs and transplanted NSCs overexpressing Nrsn1 significantly enhanced neuronal regeneration and improved functional recovery in mice subjected to middle cerebral artery occlusion and reperfusion (MCAO/R). Collectively, these findings identify Nrsn1 as a key regulator of NSC neuronal differentiation and uncover a Nrsn1–Smarcc1 coupling mechanism that promotes neural regeneration after ischemic brain injury, highlighting a potential molecular target for strategies aimed at enhancing post‐stroke recovery.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

The paper's code and data availability statement is in the Data section.

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Data

Datasets cited

Data Availability Statement

The data that support the findings of this study are available in the supplementary material of this article. The snRNA‐seq, snATAC‐seq and Stereo‐seq datasets generated in this study have been deposited at the GEO repository. Accession numbers: GSE332910; https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE332910. They are also deposited at the China National Center for Bioinformation (CNCB). Accession numbers: OMIX014345; https://ngdc.cncb.ac.cn/omix/preview/iTKW0LED. They are also deposited at figshare: https://figshare.com/s/10e8c6191b9a013d97d2; https://figshare.com/s/4c17c8a75d899e080347. The code and markdown scripts used to do the analysis in the paper have been deposited at figshare: https://figshare.com/s/4a4443e586d9151ad515. The original immunofluorescence image has been uploaded at figshare: https://figshare.com/s/af36a59aa6731ba67b3a.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, pages, dates, 19 authors, 6 keywords, 5 funders, 78 references.

Cite

This paper

Zhang, R., Liu, C., Zhou, Y., Zhao, K., Li, M., Cai, B., Wang, Y., Yuan, Z., Liu, Z., Yuan, Z., Xiao, Y., Zhou, P., Shui, K., Bao, W., Zhang, M., Qin, J., Chen, J., Yang, X., & Dong, Z. (2026). Nrsn1-Smarcc1 Coupling Regulates Neural Stem Cell Differentiation and Chronic-phase Recovery After Ischemic Stroke. Advanced science (Weinheim, Baden-Wurttemberg, Germany), e77547. https://doi.org/10.1002/advs.77547

BibTeX

@article{zhang2026nrsn1,
author = {Zhang, Ruolin and Liu, Chang and Zhou, Yuneng and Zhao, Kaichen and Li, Muyang and Cai, Bingcheng and Wang, Ying and Yuan, Zhiyuan and Liu, Zhaoxin and Yuan, Zilong and Xiao, Yao and Zhou, Peiyang and Shui, Ke and Bao, Wendai and Zhang, Min and Qin, Jun and Chen, Jun and Yang, Xin and Dong, Zhiqiang},
title = {{Nrsn1-Smarcc1 Coupling Regulates Neural Stem Cell Differentiation and Chronic-phase Recovery After Ischemic Stroke}},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
year = {2026},
month = sep,
pages = {e77547},
publisher = {Wiley},
issn = {2198-3844},
doi = {10.1002/advs.77547},
url = {https://doi.org/10.1002/advs.77547},
pmid = {42693582},
pmcid = {PMC13542395}
}

RIS

TY - JOUR
AU - Zhang, Ruolin
AU - Liu, Chang
AU - Zhou, Yuneng
AU - Zhao, Kaichen
AU - Li, Muyang
AU - Cai, Bingcheng
AU - Wang, Ying
AU - Yuan, Zhiyuan
AU - Liu, Zhaoxin
AU - Yuan, Zilong
AU - Xiao, Yao
AU - Zhou, Peiyang
AU - Shui, Ke
AU - Bao, Wendai
AU - Zhang, Min
AU - Qin, Jun
AU - Chen, Jun
AU - Yang, Xin
AU - Dong, Zhiqiang
TI - Nrsn1-Smarcc1 Coupling Regulates Neural Stem Cell Differentiation and Chronic-phase Recovery After Ischemic Stroke
T2 - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
J2 - Adv Sci (Weinh)
PY - 2026
DA - 2026/09/03
SP - e77547
SN - 2198-3844
PB - Wiley
DO - 10.1002/advs.77547
UR - https://doi.org/10.1002/advs.77547
LA - en
ER -

CSL-JSON

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