Vinh, A. | Search bioRxiv

bioRxiv2021

Self-renewing tissue-resident endothelial-macrophage progenitor cells originate from yolk sac and are a local source of inflammation and neovascularization in postnatal aorta

Converging evidence indicates that extra-embryonic yolk sac is the source of both macrophages and endothelial cells in adult mouse tissues. Prevailing views are that these embryonically derived cells are maintained after birth by proliferative self-renewal in their differentiated states. Here we identify clonogenic endothelial-macrophage (EndoMac) progenitor cells in the adventitia of embryonic and postnatal mouse aorta, that are independent of Flt3-mediated bone marrow hematopoiesis and derive from an early embryonic CX3CR1+ and CSF1R+ source. These bipotent progenitors are proliferative and vasculogenic, contributing to adventitial neovascularization and forming perfused blood vessels after transfer into ischemic tissue. We establish a regulatory role for angiotensin II, which enhances their clonogenic and differentiation properties and rapidly stimulates their proliferative expansion in vivo. Our findings demonstrate that embryonically derived EndoMac progenitors participate in local vasculogenic responses in the aortic wall by contributing to the expansion of endothelial cells and macrophages postnatally.

cell biology↗

bioRxiv2019

High-resolution transcriptomic profiling of the heart during chronic stress reveals cellular drivers of cardiac fibrosis and hypertrophy

BackgroundCardiac fibrosis is a key antecedent to many types of cardiac dysfunction including heart failure. Physiological factors leading to cardiac fibrosis have been recognized for decades. However, the specific cellular and molecular mediators that drive cardiac fibrosis, and the relative impact of disparate cell populations on cardiac fibrosis, remain unclear. MethodsWe developed a novel cardiac single-cell transcriptomics strategy to characterize the cardiac cellulome--the network of cells that forms the heart. This method was utilized to profile the cardiac cellular ecosystem in response to two weeks of continuous administration of Angiotensin II, a pro-fibrotic stimulus which drives pathological cardiac remodeling. ResultsThis analysis uncovered multiple cell populations contributing to pathological remodeling of the extracellular matrix of the heart. Two phenotypically distinct fibroblast populations emerged after induction of tissue stress to promote fibrosis in the absence of smooth muscle actin-expressing myofibroblasts, a key pro-fibrotic cell population. Further, the cellular responses to Angiotensin II and the relative abundance of fibrogenic cells were sexually dimorphic. ConclusionsThese results offer a valuable resource for exploring the cardiac cellular landscape in health and after chronic cardiovascular stress. These data provide insights into the cellular and molecular mechanisms that promote pathological remodeling of the mammalian heart, highlighting early transcriptional changes which precede chronic cardiac fibrosis.

cell biology↗