Lineage tracing clarifies the cellular origin of tissue-resident macrophages in the developing heart

Kuo Liu, Hengwei Jin, Muxue Tang, Shaohua Zhang, Xueying Tian, Mingjun Zhang, Ximeng Han, Xiuxiu Liu, Juan Tang, Wenjuan Pu, Yan Li, Lingjuan He, Zhongzhou Yang, Kathy O. Lui, Bin Zhou

Research output: Contribution to journalArticlepeer-review


Tissue-resident macrophages play essential functions in the maintenance of tissue homeostasis and repair. Recently, the endocardium has been reported as a de novo hemogenic site for the contribution of hematopoietic cells, including cardiac macrophages, during embryogenesis. These observations challenge the current consensus that hematopoiesis originates from the hemogenic endothelium within the yolk sac and dorsal aorta. Whether the developing endocardium has such a hemogenic potential requires further investigation. Here, we generated new genetic tools to trace endocardial cells and reassessed their potential contribution to hematopoietic cells in the developing heart. Fate-mapping analyses revealed that the endocardium contributed minimally to cardiac macrophages and circulating blood cells. Instead, cardiac macrophages were mainly derived from the endothelium during primitive/transient definitive (yolk sac) and definitive (dorsal aorta) hematopoiesis. Our findings refute the concept of endocardial hematopoiesis, suggesting that the developing endocardium gives rise minimally to hematopoietic cells, including cardiac macrophages.

Original languageEnglish (US)
Article numbere202108093
JournalJournal of Cell Biology
Issue number6
StatePublished - Jun 6 2022
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology


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