Expression of Stem Cell Markers in the Human Fetal KidneyReportar como inadecuado




Expression of Stem Cell Markers in the Human Fetal Kidney - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

In the human fetal kidney HFK self-renewing stem cells residing in the metanephric mesenchyme MM-blastema are induced to form all cell types of the nephron till 34th week of gestation. Definition of useful markers is crucial for the identification of HFK stem cells. Because wilms- tumor, a pediatric renal cancer, initiates from retention of renal stem cells, we hypothesized that surface antigens previously up-regulated in microarrays of both HFK and blastema-enriched stem-like wilms- tumor xenografts NCAM, ACVRIIB, DLK1-PREF, GPR39, FZD7, FZD2, NTRK2 are likely to be relevant markers. Comprehensive profiling of these putative and of additional stem cell markers CD34, CD133, c-Kit, CD90, CD105, CD24 in mid-gestation HFK was performed using immunostaining and FACS in conjunction with EpCAM, an epithelial surface marker that is absent from the MM and increases along nephron differentiation and hence can be separated into negative, dim or bright fractions. No marker was specifically localized to the MM. Nevertheless, FZD7 and NTRK2 were preferentially localized to the MM and emerging tubules <10% of HFK cells and were mostly present within the EpCAMneg and EpCAMdim fractions, indicating putative stem-progenitor markers. In contrast, single markers such as CD24 and CD133 as well as double-positive CD24+CD133+ cells comprise >50% of HFK cells and predominantly co-express EpCAMbright, indicating they are mostly markers of differentiation. Furthermore, localization of NCAM exclusively in the MM and in its nephron progenitor derivatives but also in stroma and the expression pattern of significantly elevated renal stem-progenitor genes Six2, Wt1, Cited1, and Sall1 in NCAM+EpCAM- and to a lesser extent in NCAM+EpCAM+ fractions confirmed regional identity of cells and assisted us in pinpointing the presence of subpopulations that are putative MM-derived progenitor cells NCAM+EpCAM+FZD7+, MM stem cells NCAM+EpCAM-FZD7+ or both NCAM+FZD7+. These results and concepts provide a framework for developing cell selection strategies for human renal cell-based therapies.



Autor: Sally Metsuyanim, Orit Harari-Steinberg, Ella Buzhor, Dorit Omer, Naomi Pode-Shakked, Herzl Ben-Hur, Reuvit Halperin, David Schne

Fuente: http://plos.srce.hr/



DESCARGAR PDF




Documentos relacionados