内皮细胞衍生的CX3CR1+祖细胞在心脏发生过程中产生心血管细胞。

Kyuwon Cho,Mark Andrade,S Khodayari Khodayari,Christine Lee,Seongho Bae,Sangsung Kim,Jin Eyun Kim,Young-Sup Yoon
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引用次数: 0

摘要

CX3CR1+细胞在心脏发育过程中产生组织巨噬细胞,并在成人心脏缺血损伤反应中发挥心脏保护作用。然而,CX3CR1+细胞在心脏发生过程中的起源和命运仍不清楚。在这里,我们对小鼠的CX3CR1+细胞及其后代(称为CX3CR1谱系细胞)进行了遗传谱系追踪,并证明它们在胚胎期E6.5时从外胚层细胞的一个亚群中出现,并在E7.0时形成顶壁内胚层细胞。在发育的E8.0-9.5阶段,Cx3cr1谱系细胞分别通过新生分化和与原有心肌细胞或内皮细胞融合产生心肌细胞和内皮细胞。Cx3cr1细胞系在成人心脏中持续存在,包括约13%的心肌细胞和约31%的内皮细胞。此外,从小鼠胚胎干细胞分化而来的CX3CR1+细胞在体外、离体和体内均可生成心肌细胞、内皮细胞和巨噬细胞。单细胞RNA测序显示,Cx3cr1+细胞代表了从胚胎干细胞向中胚层过渡的中间细胞群。综上所述,胚胎CX3CR1+细胞构成了一个多能的上皮细胞衍生祖细胞群,不仅有助于巨噬细胞的形成,还有助于心肌细胞和内皮细胞的形成。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Epiblast-derived CX3CR1+ progenitors generate cardiovascular cells during cardiogenesis.
CX3CR1+ cells generate tissue macrophages in the developing heart and play cardioprotective roles in response to ischemic injuries in the adult heart. However, the origin and fate of CX3CR1+ cells during cardiogenesis remain unclear. Here, we performed genetic lineage tracing of CX3CR1+ cells and their progeny (termed Cx3cr1 lineage cells) in the mouse and demonstrated that they emerge from a subset of epiblast cells at embryonic day E6.5 and contribute to the parietal endoderm cells at E7.0. At E8.0-9.5 of development, Cx3cr1 lineage cells produced cardiomyocytes and endothelial cells via both de novo differentiation and fusion with pre-existing cardiomyocytes or endothelial cells, respectively. Cx3cr1 lineage cells persisted in the adult heart, comprising ~13% of cardiomyocytes and ~31% of endothelial cells. Additionally, CX3CR1+ cells differentiated from mouse embryonic stem cells generated cardiomyocytes, endothelial cells, and macrophages in vitro, ex vivo, and in vivo. Single-cell RNA sequencing revealed that Cx3cr1+ cells represent an intermediate cell population transitioning from embryonic stem cells to mesoderm. Taken together, embryonic CX3CR1+ cells constitute a multipotent epiblast-derived progenitor population that contributes not only to the formation of macrophages, but also of cardiomyocytes and endothelial cells.
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