Activation of a NCAM1 expressing progenitor cell population in adult human kidney epithelia
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE49100 | GEO | 2013/07/23
SECONDARY ACCESSION(S): PRJNA212999
REPOSITORIES: GEO
Similar Datasets
Project description:NCAM1+ subpopulation of adult human kidney epithelial cells (hKEpC) can be specifically activated in vitro to stem-like cells that de-differentiate and recapitulate embryogenesis. We used microarrays to detail the global programme of gene expression in the NCAM1+ sub-population in comparison to NCAM1-.
2013-07-23 | E-GEOD-49100 | biostudies-arrayexpress
Project description:NCAM1+ subpopulation of fetal human kidneyl cells are nephron progenitors We used microarrays to detail the global programme of gene expression in the NCAM1+ sub-population in comparison to total culture.
2013-07-23 | E-GEOD-49101 | biostudies-arrayexpress
Project description:NCAM1+ subpopulation of fetal human kidneyl cells are nephron progenitors
2013-07-23 | GSE49101 | GEO
Project description:After acute kidney injury, mice with short telomeres develop increased damage with reduced proliferative capacity, which suggests an important role for telomere length in kidney repair. The enzyme telomerase reverse transcriptase (mTert) regulates telomere length; embryonic stem cells and certain adult stem cells express mTert, but whether cells in the adult kidney express mTert and whether these cells play a role in renal repair are unknown. Here, we found that telomerase protein and mRNA were highly enriched in renal papilla, a proposed niche of kidney stem cells. Using mTert-GFP reporter mice, we detected mTert in a subset of papillary epithelial cells comprising the collecting duct predominantly but also the loop of Henle. Approximately 5% of mTert-GFP(+) cells were label retaining, a characteristic of stem cells. mTert mRNA levels increased in renal papilla after ischemia-reperfusion injury, but genetically labeled mTert-expressing papillary cells neither divided nor migrated out of the renal papilla during kidney repair. In summary, these data suggest that cells expressing telomerase reverse transcriptase are not a progenitor-cell population, and they do not play a direct role in kidney repair.
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Project description:When assembling a nephron during development a multipotent stem cell pool becomes restricted as differentiation ensues. A faulty differentiation arrest in this process leads to transformation and initiation of a Wilms' tumor. Mapping these transitions with respective surface markers affords accessibility to specific cell subpopulations. NCAM1 and CD133 have been previously suggested to mark human renal progenitor populations. Herein, using cell sorting, RNA sequencing, in vitro studies with serum-free media and in vivo xenotransplantation we demonstrate a sequential map that links human kidney development and tumorigenesis; In nephrogenesis, NCAM1+CD133- marks SIX2+ multipotent renal stem cells transiting to NCAM1+CD133+ differentiating segment-specific SIX2- epithelial progenitors and NCAM1-CD133+ differentiated nephron cells. In tumorigenesis, NCAM1+CD133- marks SIX2+ blastema that includes the ALDH1+ WT cancer stem/initiating cells, while NCAM1+CD133+ and NCAM1-CD133+ specifying early and late epithelial differentiation, are severely restricted in tumor initiation capacity and tumor self-renewal. Thus, negative selection for CD133 is required for defining NCAM1+ nephron stem cells in normal and malignant nephrogenesis.
2016-04-01 | GSE78502 | GEO
Project description:When assembling a nephron during development a multipotent stem cell pool becomes restricted as differentiation ensues. A faulty differentiation arrest in this process leads to transformation and initiation of a Wilms' tumor. Mapping these transitions with respective surface markers affords accessibility to specific cell subpopulations. NCAM1 and CD133 have been previously suggested to mark human renal progenitor populations. Herein, using cell sorting, RNA sequencing, in vitro studies with serum-free media and in vivo xenotransplantation we demonstrate a sequential map that links human kidney development and tumorigenesis; In nephrogenesis, NCAM1+CD133- marks SIX2+ multipotent renal stem cells transiting to NCAM1+CD133+ differentiating segment-specific SIX2- epithelial progenitors and NCAM1-CD133+ differentiated nephron cells. In tumorigenesis, NCAM1+CD133- marks SIX2+ blastema that includes the ALDH1+ WT cancer stem/initiating cells, while NCAM1+CD133+ and NCAM1-CD133+ specifying early and late epithelial differentiation, are severely restricted in tumor initiation capacity and tumor self-renewal. Thus, negative selection for CD133 is required for defining NCAM1+ nephron stem cells in normal and malignant nephrogenesis. Human fetal kidney mRNA profiles of 3 cell populations (NCAM1+/CD133-, NCAM+/CD133+, NCAM-/CD133+) were generated by deep sequencing using Illumina HiSeq.
2016-04-01 | E-GEOD-78502 | biostudies-arrayexpress
Project description:To generate knockin mice that express a tamoxifen-inducible Cre recombinase from the Prg4 locus (Prg4(GFPCreERt2) mice) and to use these animals to fate-map the progeny of Prg4-positive articular cartilage cells at various ages.We crossed Prg4(GFPCreERt2) mice with Rosa26(floxlacZ) or Rosa26(mTmG) reporter strains, admin-istered tamoxifen to the double heterozygous offspring at different ages, and assayed Cre-mediated recom-bination by histochemistry and/or fluorescence microscopy.In 1-month-old mice, the expression of the Prg4(GFPCreERt2) allele mirrored the expression of endogenous Prg4 and, when tamoxifen was admin-istered for 10 days, caused Cre-mediated recombination in ?70% of the superficial-most chondrocytes. Prg4(GFPCreERt2)-expressing cells were mostly confined to the top 3 cell layers of the articular cartilage in 1-month-old mice, but descendants of these cells were located in deeper regions of the articular cartilage in aged mice. On embryonic day 17.5, Prg4(GFPCreERt2)-expressing cells were largely restricted to the superficial-most cell layer of the forming joint, yet at ?1 year, the progeny of these cells spanned the depth of the articular cartilage.Our results suggest that Prg4-expressing cells located at the joint surface in the embryo serve as a progenitor population for all deeper layers of the mature articular cartilage. Also, our findings indicate that Prg4(GFPCreERt2) is expressed by superficial chondrocytes in young mice, but expands into deeper regions of the articular cartilage as the animals age. The Prg4(GFPCreERt2) allele should be a useful tool for inducing efficient Cre-mediated recombination of loxP-flanked alleles at sites of Prg4 expression.
| S-EPMC4414823 | biostudies-literature
Project description:New nephron formation (nephrogenesis) ceases in mammals around birth and is completely absent in adults. In contrast, postembryonic nephrogenesis is well documented in the mesonephric kidneys of fishes and amphibians. The transient mesonephros in reptiles (including birds) and mammals is replaced by the metanephros during embryogenesis. Thus, one may speculate that postembryonic nephrogenesis is restricted to the mesonephric kidney. Previous reports have suggested the metanephros of non-avian reptiles (hereafter reptiles) may continually form nephrons throughout life. We investigated the presence of adult nephrogenesis in reptiles by examining adult kidneys from several species including Trachemys scripta, Chrysemys picta, Boa constrictor, Tupinambis tegu, Anolis carolinensis, and Alligator mississipiensis among others. We found that all major reptilian groups (Testudines, Crocodylia, and Squamates) showed the presence of adult nephrogenesis. The total amount of nephrogenesis varied greatly between species with turtles displaying the highest density of nephrogenesis. In contrast, we were unable to detect adult nephrogenesis in monotremes, and in the iguanid A. carolinensis. Nephron progenitor cells express the transcription factor Six2, which in mammals, becomes downregulated as the progenitor cell population is exhausted and nephrogenesis ends. Using the alligator as a model, we were able to detect Six2-positive cap mesenchyme cells in the adult kidney, which spatially correlated with areas of nephrogenesis. These results suggest that the metanephric kidney of reptiles has maintained the ability to continually grow new nephrons during postembryonic life, a process lost early in mammalian evolution, likely due to the persistence of a Six2-expressing progenitor cell population.
| S-EPMC4856328 | biostudies-literature
Project description:The number of nephrons, the functional units of the kidney, varies among individuals. A low nephron number at birth is associated with a risk of hypertension and the progression of renal insufficiency. The molecular mechanisms determining nephron number during embryogenesis have not yet been clarified. Germline knockout of bone morphogenetic protein 7 (Bmp7) results in massive apoptosis of the kidney progenitor cells and defects in early stages of nephrogenesis. This phenotype has precluded analysis of Bmp7 function in the later stage of nephrogenesis. In this study, utilization of conditional null allele of Bmp7 in combination with systemic inducible Cre deleter mice enabled us to analyze Bmp7 function at desired time points during kidney development, and to discover the novel function of Bmp7 to inhibit the precocious differentiation of the progenitor cells to nephron. Systemic knockout of Bmp7 in vivo after the initiation of kidney development results in the precocious differentiation of the kidney progenitor cells to nephron, in addition to the prominent apoptosis of progenitor cells. We also confirmed that in vitro knockout of Bmp7 in kidney explant culture results in the accelerated differentiation of progenitor population. Finally we utilized colony-forming assays and demonstrated that Bmp7 inhibits epithelialization and differentiation of the kidney progenitor cells. These results indicate that the function of Bmp7 to inhibit the precocious differentiation of the progenitor cells together with its anti-apoptotic effect on progenitor cells coordinately maintains renal progenitor pool in undifferentiated status, and determines the nephron number at birth.
| S-EPMC3753328 | biostudies-literature
Project description:The Lef/Tcf-family transcription factor Tcf3 has important roles in development, stem cell function and malignancy. Previous gain- and loss-of-function studies have suggested that Tcf3 is a mediator of self-renewal and an undifferentiated state in stem and progenitor cells in skin, but little is known of its role in other postnatal tissues. Here, we explore the distribution and behavior of Tcf3-expressing cells in several adult tissues using a novel Tcf3-CreER knock-in mouse model. By lineage tracing in dorsal skin, we verify that Tcf3-expressing cells in the hair follicle bulge are self-renewing stem cells with multilineage potential. We then demonstrate, for the first time, the presence of Tcf3-expressing cells in the basal layer of several other stratified epithelia, including the paw skin, tongue and esophagus. By lineage tracing, we demonstrate that the Tcf3-expressing population in these tissues includes persistent stem cells, transient progenitors and cells undergoing active differentiation. Our observations here suggest that the role of Tcf3 in cell-fate decision is more complex than previously appreciated and is highly dependent on cellular context.
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