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Integrin α3β1-dependent mRNA expression profile of hair bulge keratinocytes and their progeny during DMBA/TPA-mediated skin tumorigenesis

ABSTRACT: Integrin α3β1 in hair bulge population affects the tumor formation following DMBA/TPA carcinogenesis protocol, however linage tracing showed that hair bulge cells do not largely contributre to tumor mass. To investigate whether α3β1 might affect tumor promoting environment and to better understand its role in hair bulge population during skin tumorigenesis, we determined the expresison profile of hair bulge-originating keratinocytes isolted from α3β1KO and WT mice during initiation of tumorigenesis.

ORGANISM(S): Mus musculus

PROVIDER: GSE135983 | GEO | 2020/05/14

REPOSITORIES: GEO

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Integrin α3β1-dependent mRNA expression profile of hair bulge keratinocytes and their progeny during DMBA/TPA-mediated skin tumorigenesis

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Project description:The human hair follicle bulge is an important niche for keratinocyte stem cells (KSCs). Elucidation of human bulge cell biology could be facilitated by analysis of global gene expression profiles and identification of unique cell-surface markers. The lack of distinctive bulge morphology in human hair follicles has hampered studies of bulge cells and KSCs. In this study, we determined the distribution of label-retaining cells to define the human anagen bulge. Using navigated laser capture microdissection, bulge cells and outer root sheath cells from other follicle regions were obtained and analyzed with cDNA microarrays. Gene transcripts encoding inhibitors of WNT and activin/bone morphogenic protein signaling were overrepresented in the bulge, while genes responsible for cell proliferation were underrepresented, consistent with the existence of quiescent noncycling KSCs in anagen follicles. Positive markers for bulge cells included CD200, PHLDA1, follistatin, and frizzled homolog 1, while CD24, CD34, CD71, and CD146 were preferentially expressed by non-bulge keratinocytes. Importantly, CD200+ cells (CD200hiCD24loCD34loCD71loCD146lo) obtained from hair follicle suspensions demonstrated high colony-forming efficiency in clonogenic assays, indicating successful enrichment of living human bulge stem cells. The stem cell behavior of enriched bulge cells and their utility for gene therapy and hair regeneration will need to be assessed in in vivo assays.

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