Identification of molecular compartments and genetic circuitry in the developing mammalian kidney

Yu, Jing; Valerius, M. Todd; Duah, Mary; Staser, Karl; Hansard, Jennifer K.; Guo, Jinjin; McMahon, Jill A.; Vaughan, Joe; Faria, Diane; Georgas, Kylie; Rumballe, Bree; Ren, Qun; Krautzberger, A. Michaela; Junker, Jan Philipp; Thiagarajan, Rathi D; Machanick, Philip; Gray, Paul A.; Oudenaarden, Alexander van; Rowitch, David H.; Stiles, Charles D.; Ma, Qiufu; Grimmond, Sean M.; Bailey, Timothy L.; Little, Melissa H.; McMahon, Andrew P.

doi:10.1242/dev.074005

Cited by 53 publications

(56 citation statements)

References 43 publications

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“…Quantitative realtime PCR analysis (qRT-PCR) using stage-matched kidneys revealed that similar to the findings with in situ analysis, Wnt4 expression was not altered in the mutant, but other genes expressed in RVs such as Fgf8, Jag1, Mecom, Ccnd1, Pax8, Lama4 and Npy (Barak et al, 2012;Brunskill et al, 2008;Grieshammer et al, 2005;Karner et al, 2011;Thiagarajan et al, 2011;Yu et al, 2012), were increased in the mutant (Fig. 3D), supporting the evidence for unrestrained differentiation in the Sall1 mutant.…”

Section: Research Articlesupporting

confidence: 77%

Sall1 balances self-renewal and differentiation of renal progenitor cells

et al. 2014

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The formation of the proper number of functional nephrons requires a delicate balance between renal progenitor cell self-renewal and differentiation. The molecular factors that regulate the dramatic expansion of the progenitor cell pool and differentiation of these cells into nephron precursor structures (renal vesicles) are not well understood. Here we show that Sall1, a nuclear transcription factor, is required to maintain the stemness of nephron progenitor cells. Transcriptional profiling of Sall1 mutant cells revealed a striking pattern, marked by the reduction of progenitor genes and amplified expression of renal vesicle differentiation genes. These global changes in gene expression were accompanied by ectopic differentiation at E12.5 and depletion of Six2+Cited1+ cap mesenchyme progenitor cells. These findings highlight a novel role for Sall1 in maintaining the stemness of the progenitor cell pool by restraining their differentiation into renal vesicles.

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Section: Research Articlesupporting

confidence: 77%

Sall1 balances self-renewal and differentiation of renal progenitor cells

et al. 2014

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“…2B). 23 While both transcripts demonstrated this pattern, Cldn19 transcripts were detected more broadly and were also apparent in early tubular structures. These early and late tubular structures give rise to the Loop of Henle that progresses from an anlage, to a primitive loop, and then to an immature loop prior to its final differentiation.…”

Section: Multiple Claudins Are Expressed During Mouse Kidney Developmentmentioning

confidence: 90%

Claudin-7, -16, and -19 during mouse kidney development

et al. 2014

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Abbreviations: E, embryonic day; P, postnatal; FHHNC, familial hypomagnesaemia with hypercalciuria and nephrocalcinosis; nd, nephric duct; ub, ureteric bud; MET, mesenchymal to epithelial transition.Members of the claudin family of tight junction proteins are critical for establishing epithelial barriers and for the regulation of paracellular transport. To understand their roles during kidney development, we first performed RT-PCR analyses and determined that 23 claudin family members were expressed in embryonic day (E) 13.5 mouse kidneys. Based on their developmental expression and phenotypes in mouse models, we hypothesized that 3 claudin members could affect nephron formation during kidney development. Using whole mount in situ hybridization and immunohistochemistry, we demonstrated that Claudin-7 (Cldn7) was expressed in the nephric duct, the emerging ureteric bud, and in tubules derived from ureteric bud branching morphogenesis. In contrast, Claudin-16 (Cldn16) and Claudin-19 (Cldn19) were expressed at later stages of kidney development in immature renal tubules that become the Loop of Henle. To determine if a loss of these claudins would perturb kidney development, we examined newborn kidneys from mutant mouse models lacking Cldn7 or Cldn16. In both models, we noted no evidence for any congenital renal malformation and quantification of nephron number did not reveal a decrease in nephron number when compared to wildtype littermates. In summary, Cldn7, Cldn16, and Cldn19 are expressed in different epithelial lineages during kidney development. Mice lacking Cldn7 or Cldn16 do not have defects in de novo nephron formation, and this suggests that these claudins primarily function to regulate paracellular transport in the mature nephron.

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“…19 These kidney MSC-like cells displayed an immunophenotypic profile and functional properties extremely similar to mouse BM-MSCs. However, this population also displayed a kidney-specific gene expression signature, 19 including the differential expression of the collecting duct markers natriuretic peptide precursor type B, 20 Uroplakin 1b, 21 and Hoxb7. 22 The expression of such markers after extensive culture suggested epithelial origin and/or epithelial potential.…”

mentioning

confidence: 99%

Collecting Duct-Derived Cells Display Mesenchymal Stem Cell Properties and Retain Selective In Vitro and In Vivo Epithelial Capacity

Ariunbold

Suhaimi

et al. 2015

Journal of the American Society of Nephrology

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We previously described a mesenchymal stem cell (MSC)-like population within the adult mouse kidney that displays long-term colony-forming efficiency, clonogenicity, immunosuppression, and panmesodermal potential. Although phenotypically similar to bone marrow (BM)-MSCs, kidney MSC-like cells display a distinct expression profile. FACS sorting from Hoxb7/enhanced green fluorescent protein (GFP) mice identified the collecting duct as a source of kidney MSC-like cells, with these cells undergoing an epithelialto-mesenchymal transition to form clonogenic, long-term, self-renewing MSC-like cells. Notably, after extensive passage, kidney MSC-like cells selectively integrated into the aquaporin 2-positive medullary collecting duct when microinjected into the kidneys of neonatal mice. No epithelial integration was observed after injection of BM-MSCs. Indeed, kidney MSC-like cells retained a capacity to form epithelial structures in vitro and in vivo, and conditioned media from these cells supported epithelial repair in vitro. mice revealed evidence for the intercalation of a Wnt4-expressing interstitial population into the neonatal collecting duct, suggesting that such intercalation may represent a normal developmental mechanism giving rise to a distinct collecting duct subpopulation. These results extend previous observations of papillary stem cell activity and collecting duct plasticity and imply a role for such cells in collecting duct formation and, possibly, repair.

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Identification of molecular compartments and genetic circuitry in the developing mammalian kidney

Cited by 53 publications

References 43 publications

Sall1 balances self-renewal and differentiation of renal progenitor cells

Sall1 balances self-renewal and differentiation of renal progenitor cells

Claudin-7, -16, and -19 during mouse kidney development

Collecting Duct-Derived Cells Display Mesenchymal Stem Cell Properties and Retain Selective In Vitro and In Vivo Epithelial Capacity

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