Publication Name	World Journal of Stem Cells
Manuscript ID	124121
DOI	10.4252/wjsc.124121
Country	China

Category	Developmental Biology
Manuscript Type	Basic Study
Article Title	EGR1-P21 axis promotes a stromal senescence-like phenotype and impairs enteric neural crest cell migration in Hirschsprung disease
Manuscript Source	Unsolicited Manuscript
All Author List	Xue Ren, Yu Zhou, Xin-Tao Zhang, Dong Sun, Zhao Tian, Qiong-Qian Xu, Ji-Chang Han, Xi-Xi He, Chun-Can Ma, Zhen-Hua Zhang, Dong-Ming Wang and Ai-Wu Li
Funding Agency and Grant Number	Funding Agency Grant Number National Natural Science Foundation of China 82571975, 82271743
Corresponding Author	Ai-Wu Li, Chief, PhD, Professor, Department of Pediatric Surgery, Qilu Hospital of Shandong University, No. 107 Wenhua West Road, Jinan 250012, Shandong Province, China. liaiwu@qiluhospital.com
Key Words	Hirschsprung disease; Early growth response 1; CDKN1A/P21; Fibroblast senescence-like state; Extracellular matrix; Enteric neural crest cells; Intestinal fibroblast; Enteric nervous system development
Core Tip	Hirschsprung disease (HSCR) has long been studied through the lens of cell-autonomous defects in enteric neural crest cells, yet the molecular identity of non-cell-autonomous contributors has remained undefined. Here, by integrating HSCR patient colonic specimens, primary mouse embryonic intestinal fibroblasts and human fibroblast models with coculture migration assays, CUT&RUN-qPCR and dual-luciferase reporter validation, we identified a stromal early growth response 1-P21 axis as a candidate mechanism that reshapes the intestinal microenvironment to impair enteric neural crest cell migration. This work identifies fibroblast-driven senescence-like and aberrant extracellular matrix remodeling as candidate targets for microenvironment-directed intervention in HSCR.
Citation	Ren X, Zhou Y, Zhang XT, Sun D, Tian Z, Xu QQ, Han JC, He XX, Ma CC, Zhang ZH, Wang DM, Li AW. EGR1-P21 axis promotes a stromal senescence-like phenotype and impairs enteric neural crest cell migration in Hirschsprung disease. World J Stem Cells 2026; In press DOI: https://doi.org/10.4252/wjsc.124121
PDF	124121-in-press.pdf

Received	2026-06-09 08:16
Peer-Review Started	2026-06-09 08:16
First Decision by Editorial Office Director
Return for Revision	2026-07-21 06:28
Revised	2026-08-12 06:53
Publication Fee Transferred	2026-09-15 02:54
Second Decision by Editor	2026-10-12 03:04
Second Decision by Editor-in-Chief
Final Decision by Editorial Office Director	2026-11-02 03:09
Articles in Press	2026-11-02 03:09
Edit the Manuscript by Language Editor
Typeset the Manuscript

ISSN	1948-0210 (online)
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