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Molecular characterization of clonal human renal forming cells

ABSTRACT: The adult kidney replaces lost cells in-vivo via proliferation of cells functioning as committed clonal progenitors. Here we combined the generation of single cell derived clonal cultures from human adult kidney with transcriptomic analysis for molecular characterization of in-vitro clonal behavior at inception and after propagation. We discovered two types of clones; rapidly proliferating de-differentiated fibroblast-like (FL) originating from the proximal tubule and stably proliferating cuboidal epithelial-like (EL) originating from distal segments that efficiently propagate with one cell giving rise to 3.3*10(6) cells. Segment-specific clonal heterogeneity included molecular characteristics of cell-cycle, epithelial-mesenchymal transition (high NCAM1, Serpine1) and oxidative phosphorylation in FL-clones. In contrast, the more quiescent EL-clones harboring markers of mature kidney epithelia (high CD24, CDH1/E-cad, EpCAM) activate the BMP pathway. Thus, the human adult kidney harbors progenitor cell function in which segment identity and the level of epithelial maturation dictate clonal behavior and sustained renal cell formation in culture.

ORGANISM(S): Homo sapiens

PROVIDER: GSE144908 | GEO | 2020/02/07

REPOSITORIES: GEO

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Project description:Hematopoietic stem cells (HSCs) are at the basis of the hematopoietic hierarchy. Their ability to self-renew and differentiate is strictly controlled by molecular signals produced by their surrounding micorenvironments composed of stromal cells. HSCs first emerge in the AGM (Aorta Gonads Mesonephros) region, amplify in the fetal liver (FL) and are maintained in the adult bone marrow (BM). To further characterize the molecular program of the HSC niches, we have compared the global transcriptome of HSC-supportive and non-supportive stromal clones established from the AGM, FL and BM. Hematopoietic stem cells (HSCs) are at the basis of the hematopoietic hierarchy. Their ability to self-renew and differentiate is strictly controlled by molecular signals produced by their surrounding micorenvironments composed of stromal cells. HSCs first emerge in the AGM (Aorta Gonads Mesonephros) region, amplify in the fetal liver (FL) and are maintained in the adult bone marrow (BM). To further characterize the molecular program of the HSC niches, we have compared the global transcriptome of HSC-supportive line from Fetal Calvaria (OP9) and non-supportive stromal clones from fetal liver (BFC). Hematopoietic stem cells (HSCs) are at the basis of the hematopoietic hierarchy. Their ability to self-renew and differentiate is strictly controlled by molecular signals produced by their surrounding micorenvironments composed of stromal cells. HSCs first emerge in the AGM (Aorta Gonads Mesonephros) region, amplify in the fetal liver (FL) and are maintained in the adult bone marrow (BM). To further characterize the molecular program of the HSC niches, we have compared the global transcriptome of HSC-supportive and non-supportive stromal clones established from fetal liver. We took advantage of stromal clones established from the AGM, FL and BM and tested for their ability to support or not HSCs ex vivo. RNA were extracted from confluent stromal cultures or sorted cells and used for hybridization of Affymetrix (mouse gene 1.0 ST) microarrays.

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Molecular characterization of clonal human renal forming cells

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