利基
干细胞巢
生物
细胞生物学
干细胞
生态学
祖细胞
作者
Gang Li,Xiao Li,Yuka Morikawa,Francisco J. Grisanti-Canozo,Fansen Meng,Chang-Ru Tsai,Yi Zhao,Lin Liu,Jong Kim,Bing Xie,Elzbieta Klysik,Shijie Liu,Md. Abul Hassan Samee,James F. Martin
标识
DOI:10.1038/s44161-024-00428-w
摘要
After myocardial infarction (MI), mammalian hearts do not regenerate, and the microenvironment is disrupted. Hippo signaling loss of function with activation of transcriptional co-factor YAP induces heart renewal and rebuilds the post-MI microenvironment. In this study, we investigated adult renewal-competent mouse hearts expressing an active version of YAP, called YAP5SA, in cardiomyocytes (CMs). Spatial transcriptomics and single-cell RNA sequencing revealed a conserved, renewal-competent CM cell state called adult (a)CM2 with high YAP activity. aCM2 co-localized with cardiac fibroblasts (CFs) expressing complement pathway component C3 and macrophages (MPs) expressing C3ar1 receptor to form a cellular triad in YAP5SA hearts and renewal-competent neonatal hearts. Although aCM2 was detected in adult mouse and human hearts, the cellular triad failed to co-localize in these non-renewing hearts. C3 and C3ar1 loss-of-function experiments indicated that C3a signaling between MPs and CFs was required to assemble the pro-renewal aCM2, C3+ CF and C3ar1+ MP cellular triad. Using single-cell RNA sequencing, spatial transcriptomics and genetic experiments, Li et al. report that the close interaction of a specific cardiomyocyte subtype (aCM2), fibroblasts expressing the complement C3 and macrophages expressing C3ar1 was observed in pro-renewal conditions, such as regenerative neonatal hearts and hearts of adult mice overexpressing an active form of YAP in cardiomyocytes.
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