SMAD3介导人类诱导多能干细胞衍生的心外膜向心脏周细胞系祖细胞的分化。

IF 5.9 2区 医学 Q1 CELL & TISSUE ENGINEERING
Stem Cell Reports Pub Date : 2024-10-08 Epub Date: 2024-09-26 DOI:10.1016/j.stemcr.2024.08.008
Yutaro Miyoshi, Antonio Lucena-Cacace, Yu Tian, Yasuko Matsumura, Kanae Tani, Misato Nishikawa, Megumi Narita, Takeshi Kimura, Koh Ono, Yoshinori Yoshida
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引用次数: 0

摘要

了解心外膜上皮细胞向间质转化(EMT)的分子机制,特别是将细胞命运导向心外膜衍生物的机制,对于利用诱导多能干细胞(iPSC)衍生的心外膜进行再生医学至关重要。尽管转化生长因子β(TGF-β)在心外膜生物学中起着关键作用,它通过SMAD蛋白的下游信号在胚胎发育过程中协调EMT,但SMAD蛋白在心外膜中维持血管稳态或介导各种心外膜衍生细胞(EPDCs)分化的功能还不十分清楚。我们的研究揭示,独立于 TGF-β 的 SMAD3 表达可自主预测心外膜细胞的规格化和系谱维持,是促进心外膜以血管生成为导向的心脏周细胞祖细胞规格化的关键介质。这一发现揭示了 SMAD3 在人类心外膜中的新作用,尤其是在产生能增强心脏微血管血管生成的心脏周细胞祖细胞方面。这一发现为利用心外膜生物学开发更有效的心脏再生策略开辟了新途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
SMAD3 mediates the specification of human induced pluripotent stem cell-derived epicardium into progenitors for the cardiac pericyte lineage.

Understanding the molecular mechanisms of epicardial epithelial-to-mesenchymal transition (EMT), particularly in directing cell fate toward epicardial derivatives, is crucial for regenerative medicine using human induced pluripotent stem cell (iPSC)-derived epicardium. Although transforming growth factor β (TGF-β) plays a pivotal role in epicardial biology, orchestrating EMT during embryonic development via downstream signaling through SMAD proteins, the function of SMAD proteins in the epicardium in maintaining vascular homeostasis or mediating the differentiation of various epicardial-derived cells (EPDCs) is not yet well understood. Our study reveals that TGF-β-independent SMAD3 expression autonomously predicts epicardial cell specification and lineage maintenance, acting as a key mediator in promoting the angiogenic-oriented specification of the epicardium into cardiac pericyte progenitors. This finding uncovers a novel role for SMAD3 in the human epicardium, particularly in generating cardiac pericyte progenitors that enhance cardiac microvasculature angiogenesis. This insight opens new avenues for leveraging epicardial biology in developing more effective cardiac regeneration strategies.

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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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