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• W4317607566 abstract "Rationale Renin cells are essential for survival. They control the morphogenesis of the kidney arterioles, and the composition and volume of our extracellular fluid, arterial blood pressure, tissue perfusion, and oxygen delivery. It is known that renin cells and associated arteriolar cells descend from FoxD1 + progenitor cells, yet renin cells remain challenging to study due in no small part to their rarity within the kidney. As such, the molecular mechanisms underlying the differentiation and maintenance of these cells remain insufficiently understood. Objective We sought to comprehensively evaluate the chromatin states and transcription factors (TFs) that drive the differentiation of FoxD1 + progenitor cells into those that compose the kidney vasculature with a focus on renin cells. Methods and Results We isolated single nuclei of FoxD1 + progenitor cells and their descendants from FoxD1 cre/+ ; R26R-mTmG mice at embryonic day 12 (E12) (n cells =1234), embryonic day 18 (E18) (n cells =3696), postnatal day 5 (P5) (n cells =1986), and postnatal day 30 (P30) (n cells =1196). Using integrated scRNA-seq and scATAC-seq we established the developmental trajectory that leads to the mosaic of cells that compose the kidney arterioles, and specifically identified the factors that determine the elusive, myo-endocrine adult renin-secreting juxtaglomerular (JG) cell. We confirm the role of Nfix in JG cell development and renin expression, and identified the myocyte enhancer factor-2 (MEF2) family of TFs as putative drivers of JG cell differentiation. Conclusions We provide the first developmental trajectory of renin cell differentiation as they become JG cells in a single-cell atlas of kidney vascular open chromatin and highlighted novel factors important for their stage-specific differentiation. This improved understanding of the regulatory landscape of renin expressing JG cells is necessary to better learn the control and function of this rare cell population as overactivation or aberrant activity of the RAS is a key factor in cardiovascular and kidney pathologies." @default.
• W4317607566 created "2023-01-21" @default.
• W4317607566 creator A5029074504 @default.
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• W4317607566 creator A5079643437 @default.
• W4317607566 creator A5086331770 @default.
• W4317607566 creator A5090211586 @default.
• W4317607566 date "2023-01-20" @default.
• W4317607566 modified "2023-10-18" @default.
• W4317607566 title "Determinants of renin cell differentiation: a single cell epi-transcriptomics approach" @default.
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