Committing the heart The heart is a complex organ composed of multiple cell types such as cardiomyocytes and endothelial cells. Cardiovascular cells arise from Mesp1-expressing progenitor cells. Lescroart et al. performed single-cell RNA-sequencing analysis of mouse wild-type and Mesp1-deficient cardiovascular progenitor cells at early gastrulation (see the Perspective by Kelly and Sperling). When Mesp1 was eliminated, embryonic cells remained pluripotent and could not differentiate into cardiovascular progenitors. During gastrulation, the different Mesp1 progenitors rapidly became committed to a particular cell fate and heart region. Notch1 expression marked the earliest step of cardiovascular lineage segregation. Science, this issue p. 1177; see also p. 1098 Mesp1-expressing progenitor cells commit to different heart cell fates in early gastrulation. Mouse heart development arises from Mesp1-expressing cardiovascular progenitors (CPs) that are specified during gastrulation. The molecular processes that control early regional and lineage segregation of CPs have been unclear. We performed single-cell RNA sequencing of wild-type and Mesp1-null CPs in mice. We showed that populations of Mesp1 CPs are molecularly distinct and span the continuum between epiblast and later mesodermal cells, including hematopoietic progenitors. Single-cell transcriptome analysis of Mesp1-deficient CPs showed that Mesp1 is required for the exit from the pluripotent state and the induction of the cardiovascular gene expression program. We identified distinct populations of Mesp1 CPs that correspond to progenitors committed to different cell lineages and regions of the heart, identifying the molecular features associated with early lineage restriction and regional segregation of the heart at the early stage of mouse gastrulation.

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通过单细胞 RNA-seq 确定心血管谱系分离的最早步骤

致力于心脏 心脏是由多种细胞类型组成的复杂器官，例如心肌细胞和内皮细胞。心血管细胞起源于表达 Mesp1 的祖细胞。莱斯克罗特等人。在原肠胚形成早期对小鼠野生型和 Mesp1 缺陷型心血管祖细胞进行了单细胞 RNA 测序分析（参见 Kelly 和 Sperling 的观点）。当 Mesp1 被消除时，胚胎细胞保持多能性并且不能分化成心血管祖细胞。在原肠胚形成过程中，不同的 Mesp1 祖细胞迅速致力于特定的细胞命运和心脏区域。Notch1 表达标志着心血管谱系分离的最早步骤。科学，这个问题 p。1177; 另见 p. 1098 表达 Mesp1 的祖细胞在早期原肠胚形成过程中有不同的心脏细胞命运。小鼠心脏发育源于原肠胚形成过程中指定的表达 Mesp1 的心血管祖细胞 (CP)。控制 CP 早期区域和谱系分离的分子过程尚不清楚。我们对小鼠中的野生型和 Mesp1-null CP 进行了单细胞 RNA 测序。我们发现 Mesp1 CP 的群体在分子上是不同的，并且跨越外胚层细胞和后来的中胚层细胞（包括造血祖细胞）之间的连续体。Mesp1 缺陷 CP 的单细胞转录组分析表明，Mesp1 是退出多能状态和诱导心血管基因表达程序所必需的。