Tcf21 as a Founder Transcription Factor in Specifying Foxd1 Cells to the Juxtaglomerular Cell Lineage.

Renin is crucial for blood pressure regulation and electrolyte balance, and its expressing cells arise from Foxd1+ stromal progenitors. However, factors guiding these progenitors toward renin-secreting cell fate remain unclear. Tcf21, a basic helix-loop-helix (bHLH) transcription factor, is essential in kidney development.

The transcription factor TCF21 is necessary for adoption of cell fates by Foxd1+ stromal progenitors during kidney development.

Unlabelled: Normal kidney development requires the coordinated interactions between multiple progenitor cell lineages. Among these, Foxd1+ stromal progenitors are essential for nephrogenesis, giving rise to diverse cell types including the renal stroma, capsule, mesangial cells, renin cells, pericytes, and vascular smooth muscle cells (VSMCs). However, the molecular mechanisms governing their differentiation remain poorly understood.

An efficient inducible model for the control of gene expression in renin cells.

Fate mapping and genetic manipulation of renin cells have relied on either noninducible lines that can introduce the developmental effects of gene deletion or bacterial artificial chromosome transgene-based inducible models that may be prone to spurious and/or ectopic gene expression. To circumvent these problems, we generated an inducible mouse model in which is under the control of the endogenous gene, an independent marker of renin cells that is expressed in a few extrarenal tissues. We confirmed the proper expression of using ; mice in which Akr1b7/renin cells become green fluorescent protein (GFP) upon tamoxifen administration.

Inhibition of Renin Expression Is Regulated by an Epigenetic Switch From an Active to a Poised State.

Background: Renin-expressing cells are myoendocrine cells crucial for the maintenance of homeostasis. Renin is regulated by cAMP, p300 (histone acetyltransferase p300)/CBP (CREB-binding protein), and Brd4 (bromodomain-containing protein 4) proteins and associated pathways. However, the specific regulatory changes that occur following inhibition of these pathways are not clear.

Tcf21 as a Founder Transcription Factor in Specifying Foxd1 Cells to the Juxtaglomerular Cell Lineage.

Unlabelled: Renin is crucial for blood pressure regulation and electrolyte balance, and its expressing cells arise from Foxd1+ stromal progenitors. However, factors guiding these progenitors toward renin-secreting cell fate remain unclear. Tcf21, a basic helix-loop-helix (bHLH) transcription factor, is essential in kidney development.

The role of Gata3 in renin cell identity.

Renin cells are precursors for other cell types in the kidney and show high plasticity in postnatal life in response to challenges to homeostasis. Our previous single-cell RNA-sequencing studies revealed that the dual zinc-finger transcription factor , which is important for cell lineage commitment and differentiation, is expressed in mouse renin cells under normal conditions and homeostatic threats. We identified a potential Gata3-binding site upstream of the renin gene leading us to hypothesize that is essential for renin cell identity.

Renin Cells, From Vascular Development to Blood Pressure Sensing.

During embryonic and neonatal life, renin cells contribute to the assembly and branching of the intrarenal arterial tree. During kidney arteriolar development renin cells are widely distributed throughout the renal vasculature. As the arterioles mature, renin cells differentiate into smooth muscle cells, pericytes, and mesangial cells.

Cells of the renin lineage promote kidney regeneration post-release of ureteral obstruction in neonatal mice.

Aim: Ureteral obstruction leads to significant changes in kidney renin expression. It is unclear whether those changes are responsible for the progression of kidney damage, repair, or regeneration. In the current study, we aimed to elucidate the contribution of renin-producing cells (RPCs) and the cells of the renin lineage (CoRL) towards kidney damage and regeneration using a model of partial and reversible unilateral ureteral obstruction (pUUO) in neonatal mice.

Determinants of renin cell differentiation: a single cell epi-transcriptomics approach.

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 + progenitor cells, yet renin cells remain challenging to study due in no small part to their rarity within the kidney.

Comparative Studies of Renin-Null Zebrafish and Mice Provide New Functional Insights.

Background: The renin-angiotensin system is highly conserved across vertebrates, including zebrafish, which possess orthologous genes coding for renin-angiotensin system proteins, and specialized mural cells of the kidney arterioles, capable of synthesising and secreting renin.

Methods: We generated zebrafish with CRISPR-Cas9-targeted knockout of renin () to investigate renin function in a low blood pressure environment. We used single-cell (10×) RNA sequencing analysis to compare the transcriptome profiles of renin lineage cells from mesonephric kidneys of with zebrafish and with the metanephric kidneys of and mice.

Patterns of differentiation of renin lineage cells during nephrogenesis.

Developmentally heterogeneous renin-expressing cells serve as progenitors for mural, glomerular, and tubular cells during nephrogenesis and are collectively termed renin lineage cells (RLCs). In this study, we quantified different renal vascular and tubular cell types based on specific markers and assessed proliferation and de novo differentiation in the RLC population. We used kidney sections of mRenCre-mT/mG mice throughout nephrogenesis.

Renin Cell Baroreceptor, a Nuclear Mechanotransducer Central for Homeostasis.

[Figure: see text].

Renin Cells, the Kidney, and Hypertension.

Renin cells are essential for survival perfected throughout evolution to ensure normal development and defend the organism against a variety of homeostatic threats. During embryonic and early postnatal life, they are progenitors that participate in the morphogenesis of the renal arterial tree. In adult life, they are capable of regenerating injured glomeruli, control blood pressure, fluid-electrolyte balance, tissue perfusion, and in turn, the delivery of oxygen and nutrients to cells.

A primitive type of renin-expressing lymphocyte protects the organism against infections.

The hormone renin plays a crucial role in the regulation of blood pressure and fluid-electrolyte homeostasis. Normally, renin is synthesized by juxtaglomerular (JG) cells, a specialized group of myoepithelial cells located near the entrance to the kidney glomeruli. In response to low blood pressure and/or a decrease in extracellular fluid volume (as it occurs during dehydration, hypotension, or septic shock) JG cells respond by releasing renin to the circulation to reestablish homeostasis.

Phylogeny and ontogeny of the renin-angiotensin system: Current view and perspectives.

The renin-angiotensin system (RAS) evolved early among vertebrates and remains functioning throughout the vertebrate phylogeny and has adapted to various environments. The RAS is crucial for the regulation of blood pressure, fluid-electrolyte balance and tissue homeostasis. The RAS is also expressed during early ontogeny in renal and extra-renal tissues, and exerts unique vascular growth and differentiation functions.

Targeted disruption of the histone lysine 79 methyltransferase Dot1L in nephron progenitors causes congenital renal dysplasia.

The epigenetic regulator Dot1, the only known histone H3K79 methyltransferase, has a conserved role in organismal development and homoeostasis. In yeast, is required for telomeric silencing and genomic integrity. In Drosophila, Dot1 () regulates homoeotic gene expression.

Deciphering the Identity of Renin Cells in Health and Disease.

Hypotension and changes in fluid-electrolyte balance pose immediate threats to survival. Juxtaglomerular cells respond to such threats by increasing the synthesis and secretion of renin. In addition, smooth muscle cells (SMCs) along the renal arterioles transform into renin cells until homeostasis has been regained.

Ctcf is required for renin expression and maintenance of the structural integrity of the kidney.

Renin cells are crucial for the regulation of blood pressure and fluid electrolyte homeostasis. We have recently shown that renin cells possess unique chromatin features at regulatory regions throughout the genome that may determine the identity and memory of the renin phenotype. The 3-D structure of chromatin may be equally important in the determination of cell identity and fate.

Renin-Expressing Cells Require β1-Integrin for Survival and for Development and Maintenance of the Renal Vasculature.

Juxtaglomerular cells are crucial for blood pressure and fluid-electrolyte homeostasis. The factors that maintain the life of renin cells are unknown. In vivo, renin cells receive constant cell-to-cell, mechanical, and neurohumoral stimulation that maintain their identity and function.