近日，韩国浦项理工大学Jiwon Jang团队发现，ETV4是一种将细胞拥挤动力学与谱系特化联系起来的机械换能器。相关论文于2024年5月3日在线发表于国际学术期刊《自然—细胞生物学》。

据了解，机械微环境的动态变化（如细胞拥挤）会调节细胞谱系的命运以及细胞的增殖。虽然接触抑制增殖的调控机制已被广泛研究，但细胞拥挤如何诱导谱系分化仍不清楚。

附：英文原文

Title: ETV4 is a mechanical transducer linking cell crowding dynamics to lineage specification

Author: Yang, Seungbok, Golkaram, Mahdi, Oh, Seyoun, Oh, Yujeong, Cho, Yoonjae, Yoe, Jeehyun, Ju, Sungeun, Lalli, Matthew A., Park, Seung-Yeol, Lee, Yoontae, Jang, Jiwon

Issue&Volume: 2024-05-03

Abstract: Dynamic changes in mechanical microenvironments, such as cell crowding, regulate lineage fates as well as cell proliferation. Although regulatory mechanisms for contact inhibition of proliferation have been extensively studied, it remains unclear how cell crowding induces lineage specification. Here we found that a well-known oncogene, ETS variant transcription factor 4 (ETV4), serves as a molecular transducer that links mechanical microenvironments and gene expression. In a growing epithelium of human embryonic stem cells, cell crowding dynamics is translated into ETV4 expression, serving as a pre-pattern for future lineage fates. A switch-like ETV4 inactivation by cell crowding derepresses the potential for neuroectoderm differentiation in human embryonic stem cell epithelia. Mechanistically, cell crowding inactivates the integrin–actomyosin pathway and blocks the endocytosis of fibroblast growth factor receptors (FGFRs). The disrupted FGFR endocytosis induces a marked decrease in ETV4 protein stability through ERK inactivation. Mathematical modelling demonstrates that the dynamics of cell density in a growing human embryonic stem cell epithelium precisely determines the spatiotemporal ETV4 expression pattern and, consequently, the timing and geometry of lineage development. Our findings suggest that cell crowding dynamics in a stem cell epithelium drives spatiotemporal lineage specification using ETV4 as a key mechanical transducer.

DOI: 10.1038/s41556-024-01415-w

Source: https://www.nature.com/articles/s41556-024-01415-w