BMP10信號促進人多能幹細胞衍生心血管祖細胞發育為心內膜細胞
作者:
小柯機器人發布時間:2020/11/5 12:48:47
加拿大大學健康網絡Gordon M. Keller、Alexander A. Mikryukov課題組發現,BMP10信號促進人多能幹細胞(hPSC)衍生心血管祖細胞發育為心內膜細胞。相關論文在線發表在2020年11月2號出版的《細胞-幹細胞》雜誌上。
為了獲取人心臟內膜細胞,研究人員利用了hPSC衍生的內皮細胞,該細胞顯示出許多心內膜特徵,包括表達體內該譜系細胞的基因組、在體外誘導未成熟心肌細胞分化為小梁心肌、以及具有內皮向間充質細胞轉化的能力。對hPSC衍生心內膜細胞發育所需信號通路的分析確定了BMP10在該過程中的新功能。
據了解,胚胎內膜對於早期心臟的發育至關重要,因為它誘導小梁心肌(形成的第一個心臟組織)的生成,並且是構成瓣膜和部分冠狀脈管系統細胞的來源。憑藉這種分化潛能,人心臟內膜細胞可以提供獨特的治療潛能,包括工程化生物瓣膜和基於細胞的治療策略,以取代受損心臟中的冠脈血管。
附:英文原文
Title: BMP10 Signaling Promotes the Development of Endocardial Cells from Human Pluripotent Stem Cell-Derived Cardiovascular Progenitors
Author: Alexander A. Mikryukov, Amine Mazine, Bei Wei, Donghe Yang, Yifei Miao, Mingxia Gu, Gordon M. Keller
Issue&Volume: 2020-11-02
Abstract: The embryonic endocardium is essential for early heart development as it functionsto induce trabecular myocardium, the first heart tissue to form, and is the sourceof the cells that make up the valves and a portion of the coronary vasculature. Withthis potential, human endocardial cells could provide unique therapeutic opportunitiesthat include engineering biological valves and cell-based therapy strategies to replacecoronary vasculature in damaged hearts. To access human endocardial cells, we generateda human pluripotent stem cell (hPSC)-derived endothelial population that displaysmany characteristics of endocardium, including expression of the cohort of genes thatidentifies this lineage in vivo, the capacity to induce a trabecular fate in immature cardiomyocytes in vitro, and the ability to undergo an endothelial-to-mesenchymal transition. Analyses ofthe signaling pathways required for development of the hPSC-derived endocardial cellsidentified a novel role for BMP10 in the specification of this lineage from cardiovascular mesoderm.
DOI: 10.1016/j.stem.2020.10.003
Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30497-5