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Ontogeny of CD24 expression in the human fetal kidney

ABSTRACT: CD24, or heat stable antigen, is a cell surface sialoglycoprotein expressed on immature cells that disappears after the cells have reached their final differentiation stage. CD24 may be important in human embryonic kidney epithelial cell differentiation. In mice, CD24 expression is up-regulated in the early metanephros and localized to developing epithelial structures but the role and expression of CD24 in the developing human kidney has not been well described. In normal human fetal kidneys from 8 to 38 weeks gestation, CD24 expression was up-regulated and restricted to the early epithelial aggregates of the metanephric blastema and to the committed proliferating tubular epithelia of the S-shape nephron; however individual CD24+ cells were identified in the interstitium of later gestation and postnatal kidneys. In freshly isolated cells, FACS analysis demonstrated distinct CD24+ and CD24+133+ cell populations, constituting up to 16% and 14% respectively of the total cells analyzed. Isolated and expanded CD24+ clones displayed features of an epithelial progenitor cell line. Early fetal urinary tract obstruction resulted in an upregulation of CD24 expression, both in developing epithelial structures of early gestation kidneys and in the cells of the injured tubular epithelium of the later gestation kidneys. These results highlight the cell specific expression of CD24 in the developing human kidney and dysregulation in fetal urinary tract obstruction. We used microarrays to define the differences in global gene expression between obstructed and normal human fetal kidneys.

ORGANISM(S): Homo sapiens

PROVIDER: GSE18969 | GEO | 2009/11/11

SECONDARY ACCESSION(S): PRJNA121015

REPOSITORIES: GEO

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Project description:INTRODUCTION AND OBJECTIVE: Obstruction and other processes that lead to renal damage can have different effects in adult versus developing kidneys. These differences are important for understanding pathophysiology, but also could influence selection of biomarkers used for detection of renal damage that could be used to guide intervention. In mice, significant renal development occurs postnatally, providing a model for understanding kidney development. To date, gene expression changes that occur mouse kidney growth and development postnatally have been poorly characterized. We describe here a comprehensive gene expression of the developing mouse kidney based on microarray profiling. METHODS: C57BL/6 mice were sacrificed and kidneys were harvested at embryonic day E19.5, and postnatal days P1, P3, P5, P7, P10, P14, P21, P28 and P35. RNA was extracted from kidneys and transcript profiling was performed using Agilent microarrays. Transcripts that undergo abrupt transitions in expression level over the time course were identified using StepMiner analysis (Sahoo, 2007). Ingenuity pathway analysis (IPA) was used to analyze the biological function and gene networks of gene expression data. RESULTS: Transcript levels for 13645 probes (representing 12769 genes) were modulated significantly over the time course, with 6949 up-regulated and 6696 down-regulated. IPA was used to identify genetic pathways, networks and functions significantly altered over the time course. Interestingly, in days P10 to P14 gene functions significantly altered were up-regulated exclusively with the functions represented including lipid metabolism, small molecule biochemistry and molecular transport. Between days P5 to P7 down-regulated genes predominated with enriched functions including, gene expression, cell cycle, protein synthesis and embryonic development. For P14 to P21 enriched functions included DNA replication, recombination and repair, cell cycle, tissue development, cellular assembly and organization, protein trafficking and cell morphology. In the late stages (P21 to P28) functional enrichment was seen for cell-to-cell signaling, tissue development, cellular movement. CONCLUSIONS: This study provides the most comprehensive temporal survey of postnatal kidney development to date. This data set provides a framework for interpreting nephropathies, such as those induced by congenital obstruction. time series design

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Ontogeny of CD24 expression in the human fetal kidney

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