Physical crowding in 3D niche regulates neural stem cell differentiation via Cx43-mediated gap junction communication.
Overview
- Hunan Research Center of the Basic Discipline for Cell Signaling, State Key Laboratory of Chemo and Biosensing, College of Biology, Hunan University, Changsha, China
- Department of Clinical Science, Intervention and Technology, Division of Obstetrics and Gynecology, Karolinska Institute, Stockholm 14186, Sweden
Abstract
Neural stem cells (NSCs) maintain central nervous system (CNS) homeostasis through self-renewal and differentiation into neurons and glia. Although physical crowding shapes the NSC niche during CNS development, its role in fate determination remains poorly understood. We investigated how NSC crowding influences intercellular junctions and lineage specification in 2D and 3D environments. While crowding promotes neuronal differentiation in both environments, robust junctional remodeling occurred only in 3D. Specifically, 3D crowding uniquely upregulated connexin 43 (Cx43)-mediated gap-junction assembly. Pharmacological Cx43 inhibition selectively attenuated 3D crowding-induced neuronal differentiation, demonstrating that gap-junction signaling is essential for fate determination in 3D. These findings highlight that the regulatory influence of NSC crowding is dimension-dependent and mediated through Cx43 gap-junction communication. By elucidating how biophysical context integrates with intercellular signaling to guide NSC behavior, this study offers mechanistic insights into stem cell biology and informs biomimetic 3D culture systems and regenerative strategies for neural tissue repair.
Reproduced under the paper's license (CC BY), from the paper cited above.
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Data
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Data and code availability
• RNA-seq data for 2D and 3D NSC cultures have been deposited in the NCBI Gene Expression Omnibus under accession IDs GEO: GSE294177 and GEO: GSE239619, respectively. • This paper does not report original code. • Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.
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Version 1, 30 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 9 authors, 2 keywords, 4 funders, 62 references, 6 RRIDs.
Cite
This paper
Liang, Y., Wang, X., He, C., Wu, Z., Yang, J., Chen, Z., Zhang, H., Zhao, C., & Shi, L. (2026). Physical crowding in 3D niche regulates neural stem cell differentiation via Cx43-mediated gap junction communication. iScience, 29(4), 115272. https://
BibTeX
@article{liang2026physic
author = {Liang, Yuyun and Wang, Xiaonan and He, Chaoyong and Wu, Zhiyan and Yang, Jing and Chen, Ziyan and Zhang, Hexu and Zhao, Cheng and Shi, Liyang},
title = {{Physical crowding in 3D niche regulates neural stem cell differentiation via Cx43-mediated gap junction communication}},
journal = {iScience},
year = {2026},
month = mar,
volume = {29},
number = {4},
pages = {115272},
publisher = {Elsevier},
issn = {2589-0042},
doi = {10.1016/
url = {https://
pmid = {41907433},
pmcid = {PMC13019501}
}
RIS
TY - JOUR
AU - Liang, Yuyun
AU - Wang, Xiaonan
AU - He, Chaoyong
AU - Wu, Zhiyan
AU - Yang, Jing
AU - Chen, Ziyan
AU - Zhang, Hexu
AU - Zhao, Cheng
AU - Shi, Liyang
TI - Physical crowding in 3D niche regulates neural stem cell differentiation via Cx43-mediated gap junction communication
T2 - iScience
J2 - iScience
PY - 2026
DA - 2026/
VL - 29
IS - 4
SP - 115272
SN - 2589-0042
PB - Elsevier
DO - 10.1016/
UR - https://
LA - en
ER -
CSL-JSON
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"language": "en",
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