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Emory University School of Medicine

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EMBO J., 23 June 2025 | https://doi.org/10.1038/s44318-025-00488-z Epiblast-derived CX3CR1+ progenitors generate cardiovascular cells during cardiogenesis

Kyuwon Cho ¹, Mark Andrade ¹, S Khodayari Khodayari ¹, Christine Lee ¹, Seongho Bae ¹, Sangsung Kim ², Jin Eyun Kim ¹& Young-Sup Yoon ^1,2,*

¹Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA 30322, USA.
²Severance Biomedical Science Institute, Yonsei UniversityCollege of Medicine, Seoul, Republic of Korea.

^*Corresponding author: correspondence to Young-Sup Yoon

Abstract

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.

논문정보

형식Research article
게재일2025년 06월 (BRIC 등록일 2025-06-26)
연구진국내(교신)+국외 연구진
분야 생명과학 > 세포생물학

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