MBNL1-dependent alternative splicing promotes neuronal differentiation through regulation of NUMA1 exon 16 during fibroblast-to-neuron reprogramming.
Overview
- Brain Research Center and State Key Laboratory of Trauma, Burns, and Combined Injury, The Army Medical University (Third Military Medical University), Chongqing, China
- Institute of Advanced Pathology Research, Jinfeng Laboratory, Chongqing, China
Abstract
Introduction: Direct neuronal reprogramming enables the generation of neurons from somatic cells without passing through a pluripotent state, yet the post-transcriptional mechanisms that refine neuronal identity after fate induction remain poorly understood.
Methods: We examined alternative splicing during fibroblast-to-neuron reprogramming and investigated the effects of MBNL1 knockdown on neuronal phenotype, transcriptomic and splicing changes, and NUMA1 exon 16 regulation.
Results: MBNL1 knockdown establishes a distinct reprogramming state (AMmnp) characterized by enhanced neurite outgrowth and a more neuron-like differentiated phenotype, without significantly affecting conversion efficiency. Among MBNL1-dependent transcriptomic and splicing changes, NUMA1 exon 16 emerges as a key target, with exon inclusion reducing neuronal marker expression specifically in the AMmnp context, whereas exon skipping is associated with a more permissive neuronal phenotypic output.
Discussion: Together, these findings position alternative splicing as an active regulatory layer that shapes neuronal identity and phenotypic output during reprogramming, linking MBNL1-dependent splicing control to cytoskeletal remodeling and neuronal differentiation.
Reproduced under the paper's license (CC BY), from the paper cited above.
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Data
Datasets cited
- geo:GSE317293 — at NCBI GEO; found in “Data availability statement”
Data availability statement
The data presented in the study are deposited in the Gene Expression Omnibus (GEO) repository, accession number GSE317293 (https://
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
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Version 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, pages, dates, 4 authors, 5 keywords, 26 references.
Cite
This paper
Li, J., Long, Q.-S., Zhang, R.-Q., & Zhu, B.-L. (2026). MBNL1-dependent alternative splicing promotes neuronal differentiation through regulation of NUMA1 exon 16 during fibroblast-to-neuron reprogramming. Frontiers in cell and developmental biology, 14, 1862147. https://
BibTeX
@article{li2026mbnl1,
author = {Li, Jun and Long, Qiu-Shuang and Zhang, Ruo-Qi and Zhu, Bing-Lin},
title = {{MBNL1-dependent alternative splicing promotes neuronal differentiation through regulation of NUMA1 exon 16 during fibroblast-to-neuron reprogramming}},
journal = {Frontiers in cell and developmental biology},
year = {2026},
month = jun,
volume = {14},
pages = {1862147},
publisher = {Frontiers Media SA},
issn = {2296-634X},
doi = {10.3389/
url = {https://
pmid = {42440601},
pmcid = {PMC13333663}
}
RIS
TY - JOUR
AU - Li, Jun
AU - Long, Qiu-Shuang
AU - Zhang, Ruo-Qi
AU - Zhu, Bing-Lin
TI - MBNL1-dependent alternative splicing promotes neuronal differentiation through regulation of NUMA1 exon 16 during fibroblast-to-neuron reprogramming
T2 - Frontiers in cell and developmental biology
J2 - Front Cell Dev Biol
PY - 2026
DA - 2026/
VL - 14
SP - 1862147
SN - 2296-634X
PB - Frontiers Media SA
DO - 10.3389/
UR - https://
LA - en
ER -
CSL-JSON
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