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Published on: July 2, 2020
Identifying the molecular phenotype of renal progenitor cells
Grant A Challen1, Gemma Martinez, Melissa J Davis
1Institute For Molecular Bioscience, Queensland Bioscience Precinct, 306 Carmody Road, The University of Queensland, St. Lucia, Brisbane, QLD, 4072, Australia.
Abstract:
Although many of the molecular interactions in kidney development are now well understood, the molecules involved in the specification of the metanephric mesenchyme from surrounding intermediate mesoderm and, hence, the formation of the renal progenitor population are poorly characterized. In this study, cDNA microarrays were used to identify genes enriched in the murine embryonic day 10.5 (E10.5) uninduced metanephric mesenchyme, the renal progenitor population, in comparison with more rostral derivatives of the intermediate mesoderm. Microarray data were analyzed using R statistical software to determine accurately genes differentially expressed between these populations. Microarray outliers were biologically verified, and the spatial expression pattern of these genes at E10.5 and subsequent stages of early kidney development was determined by RNA in situ hybridization. This approach identified 21 genes preferentially expressed by the E10.5 metanephric mesenchyme, including Ewing sarcoma homolog, 14-3-3 theta, retinoic acid receptor-alpha, stearoyl-CoA desaturase 2, CD24, and cadherin-11, that may be important in formation of renal progenitor cells. Cell surface proteins such as CD24 and cadherin-11 that were strongly and specifically expressed in the uninduced metanephric mesenchyme and mark the renal progenitor population may prove useful in the purification of renal progenitor cells by FACS. These findings may assist in the isolation and characterization of potential renal stem cells for use in cellular therapies for kidney disease.
Insights
Researchers identified 21 genes, including CD24 and cadherin-11, crucial for renal progenitor cell formation during kidney development. These cell surface proteins may aid in isolating renal stem cells for disease therapies.
Area of Science:
- Developmental Biology
- Genetics
- Molecular Biology
Background:
- The molecular mechanisms initiating kidney progenitor cell formation from intermediate mesoderm remain largely unknown.
- Understanding renal progenitor specification is key to addressing kidney disease.
Purpose of the Study:
- To identify genes involved in the early specification of the metanephric mesenchyme, the source of renal progenitor cells.
- To characterize novel molecular markers for renal progenitor populations.
Main Methods:
- Utilized cDNA microarrays to compare gene expression in embryonic day 10.5 (E10.5) metanephric mesenchyme versus other intermediate mesoderm derivatives.
- Analyzed microarray data using R statistical software for differential gene expression.
- Verified microarray findings through biological validation and RNA in situ hybridization to determine spatial expression patterns.
Main Results:
- Identified 21 genes preferentially expressed in the E10.5 metanephric mesenchyme.
- Key genes identified include Ewing sarcoma homolog, 14-3-3 theta, retinoic acid receptor-alpha, stearoyl-CoA desaturase 2, CD24, and cadherin-11.
- Cell surface proteins CD24 and cadherin-11 were highly specific markers for the renal progenitor population.
Conclusions:
- The identified genes, particularly CD24 and cadherin-11, are potentially critical for renal progenitor cell formation.
- These markers may facilitate the isolation and purification of renal progenitor cells using Fluorescence-Activated Cell Sorting (FACS).
- Findings could advance the isolation and characterization of renal stem cells for therapeutic applications in kidney disease.
