RRC ID 60710
著者 Jin Z, Chen J, Huang H, Wang J, Lv J, Yu M, Guo X, Zhang Y, Cai T, Xi R.
タイトル The Drosophila Ortholog of Mammalian Transcription Factor Sox9 Regulates Intestinal Homeostasis and Regeneration at an Appropriate Level.
ジャーナル Cell Rep
Abstract Balanced stem cell self-renewal and differentiation is essential for maintaining tissue homeostasis, but the underlying mechanisms are poorly understood. Here, we identified the transcription factor SRY-related HMG-box (Sox) 100B, which is orthologous to mammalian Sox8/9/10, as a common target and central mediator of the EGFR/Ras and JAK/STAT signaling pathways that coordinates intestinal stem cell (ISC) proliferation and differentiation during both normal epithelial homeostasis and stress-induced intestinal repair in Drosophila. The two stress-responsive pathways directly regulate Sox100B transcription via two separate enhancers. Interestingly, an appropriate level of Sox100B is critical for its function, as its depletion inhibits ISC proliferation via cell cycle arrest, while its overexpression also inhibits ISC proliferation by directly suppressing EGFR expression and additionally promotes ISC differentiation by activating a differentiation-promoting regulatory circuitry composed of Sox100B, Sox21a, and Pdm1. Thus, our study reveals a Sox family transcription factor that functions as a stress-responsive signaling nexus that ultimately controls tissue homeostasis and regeneration.
巻・号 31(8)
ページ 107683
公開日 2020-5-26
DOI 10.1016/j.celrep.2020.107683
PII S2211-1247(20)30636-7
PMID 32460025
MeSH Animals Cell Differentiation Cell Proliferation Drosophila Drosophila Proteins / metabolism* Homeostasis Intestines / physiopathology* Regeneration SOX9 Transcription Factor / metabolism*
IF 8.109
引用数 0
リソース情報
ショウジョウバエ 15552R-2