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1.
Figure 7.

Figure 7. From: Genes that Confer the Identity of the Renin Cell.

The bivalent endocrine-contractile phenotype of JG cells and homeostatic control. See text for details.

Eric W. Brunskill, et al. J Am Soc Nephrol. 2011 December;22(12):2213-2225.
2.
Figure 6.

Figure 6. From: Genes that Confer the Identity of the Renin Cell.

Localization of binding sites conserved in mice and humans for transcription factors enriched in JG cells. (A) The renin promoter and (B) the renin enhancer. See also Supplementary Table 4.

Eric W. Brunskill, et al. J Am Soc Nephrol. 2011 December;22(12):2213-2225.
3.
Figure 3.

Figure 3. From: Genes that Confer the Identity of the Renin Cell.

Akr1b7 expression is an independent marker of renin cells. Immunostaining for Akr1b7 (A, C, E, G) and renin (B, D, F, H), in consecutive sections, shows colocalization of Akr1b7 in renin cells in (A, B) newborn kidney. Short arrow, JG cells; long arrows, arterioles and larger vessel. (C, D) Adult kidney. Arrows, JG cells. Akr1b7 marks renin cells at all stages of development. (E, F) Adult kidney from an animal administered low sodium diet + captopril stimulates re-expression of renin and Akr1b7. Arrows, JG cells and afferent arteriole. Akr1b7 is expressed in the same pattern as renin. (G, H) Ren1c knockout kidney:Akr1b7 marks renin cells even although the cells are unable to make renin. Arrows in (H) indicate JG cells and afferent arterioles that are expressing Akr1b7 in (G).

Eric W. Brunskill, et al. J Am Soc Nephrol. 2011 December;22(12):2213-2225.
4.
Figure 5.

Figure 5. From: Genes that Confer the Identity of the Renin Cell.

Gene network characteristic of the adult renin cell. (A) Renin cell genes known to be involved in muscle contraction. Some of the 369 adult renin cell signature set of genes are shown in the center hexagons, with surrounding rectangles representing biologic processes (dark green), molecular functions (light green), and transcription factors (violet), with associated genes connected by lines. Genes involved in muscle contraction are highlighted in yellow. (B) Genes involved in calcium homeostasis are highlighted in yellow. (C) Transcription factors (SRF, E2A, IK3) and the smooth muscle phenotype. SRF candidate target genes are highlighted in yellow. See also Supplementary Table 3.

Eric W. Brunskill, et al. J Am Soc Nephrol. 2011 December;22(12):2213-2225.
5.
Figure 2.

Figure 2. From: Genes that Confer the Identity of the Renin Cell.

The transcriptome of renin cells is vastly different from any other renal cell type. (A) Heatmap of 1051 probesets, showing differential expression in adult total kidney cortex (Ctx) and renin expressing cells from newborn (P0), adult, and captopril-treated adults (Cap). Each horizontal line represents one probeset expression, with red showing high-level expression. (B) Heatmap of renin cell-enriched genes, comparing across multiple cell types. Developmental times are given (E10.5, E13.5, Adult, P0, P1, P2, P3, P4, E15.5), as are tissue compartment (Ub, ureteric bud; Tr, trunk; Pod, podocyte; CM, cap mesenchyme; RV, renal vesicle; Endo, endothelial cells; M Endo, medullary endothelial cells; G Endo, glomerular endothelial cells; C Endo, cortical endothelial cells; Glom, glomerulus; Mes, mesangial cells; Ren, renin-expressing cells; Cap Ren, renin cells from captopril-treated adult; Ctx, total renal cortex). (C) Heatmap of 369 most specific adult renin cell genes, derived from both single cell analysis (SCAMP) and RiboSpia analysis. Ctx, total kidney cortex; Ad, adult renin cells; P0, newborn renin cells; Cap, adult captopril-treated renin cells. See also Supplementary Figure 1 and Supplementary Tables 1, 2, and 3.

Eric W. Brunskill, et al. J Am Soc Nephrol. 2011 December;22(12):2213-2225.
6.
Figure 4.

Figure 4. From: Genes that Confer the Identity of the Renin Cell.

Genes identified in the JG cell signature are expressed in JG cells and vessels. (A–D) In situ hybridization in newborn kidneys. (A) Mef2c expression in developing vessel (arrow). (B) Hey1 is expressed in the vessels (arrows) and in glomeruli of the nephrogenic zone. (C) Nr4a1 expression in an afferent arteriole (arrow). (D) Nkx3–1 is expressed in JG cells and afferent arteriole (arrow, G, glomerulus). (E) Immunostaining shows that Nkx3–1 localizes to JG cells and the afferent arteriole in kidney of a captopril-treated adult (arrow). (F–O) Immunostaining in adult kidneys. (F) Nfat is expressed in JG cells (arrow), vessels (short arrows), and some tubules. (G) Creb is expressed in renin-expressing JG cells (outline). (H) Consecutive section of (G) showing renin expression (outline). (I) Notch3 (brown) is expressed in JG cells. (L) Double staining for Notch3 (brown) and renin (purple) in a consecutive section of (I) shows coincidence of expression. Arrows in (I) and (L), JG cells. (J) Costaining for αSMA (purple) and renin (brown) shows expression of αSMA in JG cells as well as afferent arterioles. (K) Renin expression in JG cells for comparison with (J) Arrows in (J) and (K), JG cells. (M, N) Crip1 localizes to renin expressing JG cells as well as some tubules. Arrows in (M) and (N), JG cells. (O) S1P receptor is expressed in JG cells (arrow). (P) RT-PCR of RNA extracted from FACS isolated YFP+ cells confirms the expression of Akr1b7 and RBP-J mRNAs. (Q) Chromatin immunoprecipitation shows enrichment of phopspho-Creb at the cAMP responsive element in the renin enhancer in renin-expressing kidney cortex cells but not in skeletal muscle cells, which do not express renin. (R) RBP-J is enriched at the RBP-J element in cells from primary cultures of kidney arterial smooth muscle cells.

Eric W. Brunskill, et al. J Am Soc Nephrol. 2011 December;22(12):2213-2225.
7.
Figure 1.

Figure 1. From: Genes that Confer the Identity of the Renin Cell.

As the kidney matures, renin cells are restricted to the classical juxtaglomerular localization. (A) Top: Schematic representation of the distribution of renin cells (RC depicted in yellow) during early development (left) and the progressive restriction in the location of RCs to the JGA (right) during kidney ontogeny. If an adult animal is subjected to a condition that threatens BP and/or fluid-electrolyte homeostasis, there is a recruitment of RCs along the afferent and interlobular arterioles, and within the glomeruli—by dedifferentiation of smooth muscle cells (SMC, red) and glomerular mesangial cells to renin-expressing cells—in a pattern resembling the embryonic and fetal stages of renin distribution. Bottom: Classical depiction of the circulating renin angiotensin system and its acknowledged functions. EC, endothelial cell depicted in blue; C, capillaries; Ang I, angiotensin I; Ang II, angiotensin II; ACE, angiotensin converting enzyme; Na, sodium. (B) Development of the nephron and its vasculature. Upon induction by the dividing ureteric tip, the mesenchymal cells around it condensate to form the cap mesenchyme (CM), which, upon differentiation, evolves into the renal vesicle (RV) the s-shaped body (S), glomerulus (G), and the proximal tubule (PT). The JG cells and arterioles originate from a separate group of mesenchymal precursors that differentiate in situ to form the afferent and efferent arterioles, (aa) and (ea), respectively. The distribution of renin cells in the immature kidney shown on the left is extensive along the aa, interlobular arterioles, and arcuate arteries. H, loop of Henle; MD, macula densa; DT, distal tubule.

Eric W. Brunskill, et al. J Am Soc Nephrol. 2011 December;22(12):2213-2225.

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