Embryonic Immune Cells Remodel the Heart

Grainger, Stephanie; Traver, David

doi:10.1016/j.devcel.2019.02.017

Cited by 3 publications

(4 citation statements)

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“…Collectively, by using more specific genetic tools that distinguished endocardial cells from endothelial cells of YS and AGM, we demonstrated that the endocardium was not hemogenic and did not give rise to cardiac macrophages or other circulating blood cells. The macrophages that have been reported as essential for valvular remodeling ( Grainger and Traver, 2019 ; Kim et al, 2021 ; Shigeta et al, 2019 ) were more likely derived from the Nfatc1-Cre –labeled endothelial cells of YS or AGM. How these cardiac macrophages are recruited from the circulation and adopt new functions in the developing heart merits further investigation.…”

Section: Discussionmentioning

confidence: 98%

“…The inducible drivers are limited by incomplete recombination, so it is still possible that the lineage-negative endocardial cells were hemogenic, as the Npr3-CreER did not label all endocardial cells, and the Npr3-CreER randomly labeled the vast majority of endocardial cells (>90%) in this study. Therefore, these fate-mapping data may raise great concern about data interpretation regarding the concept of hemogenic endocardium in previous studies ( Grainger and Traver, 2019 ; Nakano et al, 2013 ; Shigeta et al, 2019 ; Zamir et al, 2017 ). However, in our ex vivo hematopoietic colony-forming assays, we isolated the whole-heart tissues that were unable to contribute to any macrophage colony.…”

Section: Discussionmentioning

confidence: 98%

“…Therefore, hematopoietic stem and progenitor cells and all blood cell lineages specifically originate from HE. Identification of new regions containing HE will reshape our current concept of hematopoiesis and provide valuable information to study tissue homeostasis and inflammation ( Grainger and Traver, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

“…Recent studies have suggested that the endocardium contributes to transient definitive hematopoiesis in the developing heart ( Grainger and Traver, 2019 ; Nakano et al, 2013 ; Shigeta et al, 2019 ; Zamir et al, 2017 ). Specifically, Nkx2.5 + endocardium-derived definitive EMPs emerge at ∼E9.5 that could enter the peripheral circulation during embryogenesis ( Nakano et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

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

Liu

Jin

Tang

et al. 2022

Journal of Cell Biology

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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.

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Section: Discussionmentioning

confidence: 98%