加拿大多伦多大学Gordon M. Keller、Donghe Yang等研究人员合作利用多能干细胞模拟人类多谱系心区发育。相关论文于2022年9月1日发表在《细胞—干细胞》杂志上。

Title: Modeling human multi-lineage heart field development with pluripotent stem cells

Author: Donghe Yang, Juliana Gomez-Garcia, Shunsuke Funakoshi, Thinh Tran, Ian Fernandes, Gary D. Bader, Michael A. Laflamme, Gordon M. Keller

Issue&Volume: 2022/09/01

Abstract: The cardiomyocyte (CM) subtypes in the mammalian heart derive from distinct lineages known as the first heart field (FHF), the anterior second heart field (aSHF), and the posterior second heart field (pSHF) lineages that are specified during gastrulation. We modeled human heart field development from human pluripotent stem cells (hPSCs) by using single-cell RNA-sequencing to delineate lineage specification and progression. Analyses of hPSC-derived and mouse mesoderm transcriptomes enabled the identification of distinct human FHF, aSHF, and pSHF mesoderm subpopulations. Through staged manipulation of signaling pathways identified from transcriptomics, we generated myocyte populations that display molecular characteristics of key CM subtypes. The developmental trajectory of the human cardiac lineages recapitulated that of the mouse, demonstrating conserved cardiovascular programs. These findings establish a comprehensive landscape of human embryonic cardiogenesis that provides access to a broad spectrum of cardiomyocytes for modeling congenital heart diseases and chamber-specific cardiomyopathies as well as for developing new therapies to treat them.

DOI: 10.1016/j.stem.2022.08.007

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(22)00343-5