Activation of a transient progenitor state in the epicardium is required for zebrafish heart regeneration.
Activation of a transient progenitor state in the epicardium is required for zebrafish heart regeneration.
复制标题
斑马鱼心脏再生需要心外膜瞬时祖细胞状态的激活。
DOI：
10.1038/s41467-022-35433-9
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发表时间：
2022-12-13
影响因子：
16.6
通讯作者：
Cao, Jingli
中科院分区：
文献类型：
--
作者：
Xia, Yu;Duca, Sierra;Perder, Bjorn;Dundar, Friederike;Zumbo, Paul;Qiu, Miaoyan;Yao, Jun;Cao, Yingxi;Harrison, Michael R. M.;Zangi, Lior;Betel, Doron;Cao, Jingli
心外膜是一种包绕脊椎动物心脏的间皮细胞组织，通过旁分泌作用支持损伤后的心脏再生，并作为多能祖细胞的来源。然而，成人心外膜中的祖细胞状态尚未确定。通过对未损伤和再生的成年斑马鱼心脏分离的心外膜细胞进行单细胞RNA测序，我们确定了心外膜的上皮亚群和间叶亚群。我们进一步鉴定了一个瞬时激活的心外膜祖细胞(AEPC)亚群，以ptx3a和col12a1b的表达为标志。在心脏损伤时，aEPC从上皮心外膜出来，迁移到伤口周围，经历上皮-间充质转化(EMT)，并分化为壁细胞和PDGFRA+hapln1a+间充质心外膜细胞。这些转导和分化过程受转化生长因子β途径的调控。有条件地消融aEPC通过减少NRG1的表达和间充质细胞数量来阻止心脏再生。我们的发现确定了对心脏再生不可或缺的成人心外膜的暂时性祖细胞群体，并强调它是加强心脏修复的潜在靶点。心外膜支持心脏再生，但具体是如何进行的尚不清楚。在这里，作者将激活的心外膜祖细胞群体定义为斑马鱼心脏成功再生所需的基本细胞类型和旁分泌因子的来源。
The epicardium, a mesothelial cell tissue that encompasses vertebrate hearts, supports heart regeneration after injury through paracrine effects and as a source of multipotent progenitors. However, the progenitor state in the adult epicardium has yet to be defined. Through single-cell RNA-sequencing of isolated epicardial cells from uninjured and regenerating adult zebrafish hearts, we define the epithelial and mesenchymal subsets of the epicardium. We further identify a transiently activated epicardial progenitor cell (aEPC) subpopulation marked by ptx3a and col12a1b expression. Upon cardiac injury, aEPCs emerge from the epithelial epicardium, migrate to enclose the wound, undergo epithelial-mesenchymal transition (EMT), and differentiate into mural cells and pdgfra+hapln1a+ mesenchymal epicardial cells. These EMT and differentiation processes are regulated by the Tgfβ pathway. Conditional ablation of aEPCs blocks heart regeneration through reduced nrg1 expression and mesenchymal cell number. Our findings identify a transient progenitor population of the adult epicardium that is indispensable for heart regeneration and highlight it as a potential target for enhancing cardiac repair. The epicardium supports heart regeneration, though precisely how is unclear. Here the authors define an activated epicardial progenitor population as the source of essential cell types and paracrine factors for successful heart regeneration in zebrafish.
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影响因子：
2.7
作者：
Bertozzi, Alberto;Wu, Chi-Chung;Weidinger, Gilbert
通讯作者：
Weidinger, Gilbert
影响因子：
46.9
作者：
Becht, Etienne;McInnes, Leland;Newell, Evan W.
通讯作者：
Newell, Evan W.
影响因子：
64.8
作者：
Cao, Junyue;Spielmann, Malte;Shendure, Jay
通讯作者：
Shendure, Jay
影响因子：
48
作者：
Amezquita, Robert A.;Lun, Aaron T. L.;Hicks, Stephanie C.
通讯作者：
Hicks, Stephanie C.
DOI：
10.1002/wsbm.1367
发表时间：
2017-01
期刊：
Wiley interdisciplinary reviews. Systems biology and medicine
影响因子：
--
作者：
Hadas Y;Katz MG;Bridges CR;Zangi L
通讯作者：
Zangi L