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RNA-seq of cardiac lineage cells (day 3 of cardiac differentiation) derived from human embryonic stem cells (hESCs) overexpressed with Monkeypox virus-protein revealed the effects of H3L and A29L in human cardiac development.

ABSTRACT: Monkeypox virus (MPV) can infect human cells and induces injuries in human. However, whether and how MPV affect the function of human cells remain to be elucidated. Here, we overexpressed H3L and A29L in hESCs, separately. We appliced RNA-seq on cardiac lineage cells (day 3 of cardiac differentiation) derived from human embryonic stem cells (hESCs) overexpressed with Monkeypox virus-proteins (Control, H3L and A29L) and want to know gene expression patterns of control and overexpression cell lines. Subsequent data analyses will help us to know whether and how H3L and A29L affect human cardiac development.

ORGANISM(S): Homo sapiens

PROVIDER: GSE239712 | GEO | 2024/08/28

REPOSITORIES: GEO

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Project description:The first macrophages that seed the developing heart originate from the yolk sac during fetal life. While murine studies reveal important homeostatic and reparative functions in adults, we know little about their roles in the earliest stages of human heart development due to a lack of accessible tissue. Generation of bioengineered human cardiac microtissues from pluripotent stem cells models these first steps in cardiac tissue development, however macrophages have not been included in these studies. To bridge these gaps, we differentiated human embryonic stem cells (hESCs) into primitive LYVE1+ macrophages (hESC-macrophages; akin to yolk sac macrophages) that stably engrafted within cardiac microtissues composed of hESC-cardiomyocytes and fibroblasts to study reciprocal interactions. Engraftment induced a tissue resident macrophage gene program resembling human fetal cardiac macrophages, enriched in efferocytic pathways. Functionally, hESC-macrophages induced production and maturation of cardiomyocyte sarcomeric proteins, and enhanced contractile force, relaxation kinetics, and electrical properties. Mechanistically, the primary effect of hESC-macrophages was during the stressful events surrounding early microtissue formation, where they engaged in phosphatidylserine dependent ingestion of apoptotic cardiomyocyte cargo, which reinforced core resident macrophage identity, reduced microtissue stress and drove hESC-cardiomyocytes to become more similar to human ventricular cardiomyocytes found in early development, both transcriptionally and metabolically. Inhibiting efferocytosis of hESC-cardiomyocytes by hESC-macrophages led to increased cell stress, impaired sarcomeric protein maturation and reduced cardiac microtissue function (contraction and relaxation). Taken together, macrophage-engineered human cardiac microtissues represent a considerably improved model for human heart development, and reveal a major beneficial, yet previously unappreciated role for human primitive macrophages in enhancing cardiac tissue function.

Dataset Information

RNA-seq of cardiac lineage cells (day 3 of cardiac differentiation) derived from human embryonic stem cells (hESCs) overexpressed with Monkeypox virus-protein revealed the effects of H3L and A29L in human cardiac development.

Similar Datasets

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