ERK5促进自分泌表达,以维持人类多能干细胞中细胞命运规范的有丝分裂平衡。

IF 5.9 2区 医学 Q1 CELL & TISSUE ENGINEERING
Stem Cell Reports Pub Date : 2024-09-10 Epub Date: 2024-08-15 DOI:10.1016/j.stemcr.2024.07.007
Chengcheng Song, Zhaoying Zhang, Dongliang Leng, Ziqing He, Xuepeng Wang, Weiwei Liu, Wensheng Zhang, Qiang Wu, Qi Zhao, Guokai Chen
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引用次数: 0

摘要

人类多能干细胞(hPSCs)的稳态需要细胞外因子的信号平衡。细胞培养基中的外源调节因子已被广泛报道,但很少有人关注来自 hPSC 自身的自分泌因子。在本报告中,我们证明细胞外信号相关激酶 5(ERK5)可调节多能性和分化所必需的内源性自分泌因子。在成纤维细胞生长因子2(FGF2)和转化生长因子β(TGF-β)存在的情况下,抑制ERK5可使hPSCs自我更新,但NANOG的表达受到部分抑制。进一步的分析表明,ERK5 可促进 NODAL、FGF8 和 WNT3 等自分泌因子的表达。添加 NODAL 蛋白可挽救 ERK5 抑制下的 NANOG 表达和分化表型。我们证明,即使没有必需的生长因子FGF2和TGF-β,组成型活性ERK5通路也能实现自我更新。这项研究强调了自分泌途径对正常维持和分化的重要贡献。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
ERK5 promotes autocrine expression to sustain mitogenic balance for cell fate specification in human pluripotent stem cells.

The homeostasis of human pluripotent stem cells (hPSCs) requires the signaling balance of extracellular factors. Exogenous regulators from cell culture medium have been widely reported, but little attention has been paid to the autocrine factor from hPSCs themselves. In this report, we demonstrate that extracellular signal-related kinase 5 (ERK5) regulates endogenous autocrine factors essential for pluripotency and differentiation. ERK5 inhibition leads to erroneous cell fate specification in all lineages even under lineage-specific induction. hPSCs can self-renew under ERK5 inhibition in the presence of fibroblast growth factor 2 (FGF2) and transforming growth factor β (TGF-β), although NANOG expression is partially suppressed. Further analysis demonstrates that ERK5 promotes the expression of autocrine factors such as NODAL, FGF8, and WNT3. The addition of NODAL protein rescues NANOG expression and differentiation phenotypes under ERK5 inhibition. We demonstrate that constitutively active ERK5 pathway allows self-renewal even without essential growth factors FGF2 and TGF-β. This study highlights the essential contribution of autocrine pathways to proper maintenance and differentiation.

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来源期刊
Stem Cell Reports
Stem Cell Reports CELL & TISSUE ENGINEERING-CELL BIOLOGY
CiteScore
10.50
自引率
1.70%
发文量
200
审稿时长
28 weeks
期刊介绍: Stem Cell Reports publishes high-quality, peer-reviewed research presenting conceptual or practical advances across the breadth of stem cell research and its applications to medicine. Our particular focus on shorter, single-point articles, timely publication, strong editorial decision-making and scientific input by leaders in the field and a "scoop protection" mechanism are reasons to submit your best papers.
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