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Transcriptional profiling of putative human epithelial stem cells.

Koçer SS, Djurić PM, Bugallo MF, Simon SR, Matic M - BMC Genomics (2008)

Bottom Line: This study demonstrates that alpha 6+/MHCI- cells have additional characteristics attributed to stem cells.Our study is important for understanding self renewal and differentiation of epidermal stem cells, and for elucidating signaling pathways involved in those processes.The generated data base may serve those working with other human epithelial tissue progenitors.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biochemistry and Cell Biology, State University of New York at Stony Brook, Stony Brook, NY, USA. Salih.Kocer@yale.edu

ABSTRACT

Background: Human interfollicular epidermis is sustained by the proliferation of stem cells and their progeny, transient amplifying cells. Molecular characterization of these two cell populations is essential for better understanding of self renewal, differentiation and mechanisms of skin pathogenesis. The purpose of this study was to obtain gene expression profiles of alpha 6+/MHCI+, transient amplifying cells and alpha 6+/MHCI-, putative stem cells, and to compare them with existing data bases of gene expression profiles of hair follicle stem cells. The expression of Major Histocompatibility Complex (MHC) class I, previously shown to be absent in stem cells in several tissues, and alpha 6 integrin were used to isolate MHCI positive basal cells, and MHCI low/negative basal cells.

Results: Transcriptional profiles of the two cell populations were determined and comparisons made with published data for hair follicle stem cell gene expression profiles. We demonstrate that presumptive interfollicular stem cells, alpha 6+/MHCI- cells, are enriched in messenger RNAs encoding surface receptors, cell adhesion molecules, extracellular matrix proteins, transcripts encoding members of IFN-alpha family proteins and components of IFN signaling, but contain lower levels of transcripts encoding proteins which take part in energy metabolism, cell cycle, ribosome biosynthesis, splicing, protein translation, degradation, DNA replication, repair, and chromosome remodeling. Furthermore, our data indicate that the cell signaling pathways Notch1 and NF-kappaB are downregulated/inhibited in MHC negative basal cells.

Conclusion: This study demonstrates that alpha 6+/MHCI- cells have additional characteristics attributed to stem cells. Moreover, the transcription profile of alpha 6+/MHCI- cells shows similarities to transcription profiles of mouse hair follicle bulge cells known to be enriched for stem cells. Collectively, our data suggests that alpha 6+/MHCI- cells may be enriched for stem cells. This study is the first comprehensive gene expression profile of putative human epithelial stem cells and their progeny that were isolated directly from neonatal foreskin tissue. Our study is important for understanding self renewal and differentiation of epidermal stem cells, and for elucidating signaling pathways involved in those processes. The generated data base may serve those working with other human epithelial tissue progenitors.

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Changes in the gene expression during epidermal differentiation. (A) Genes that are gradually downregulated, or upregulated during epidermal differentiation. The EST* represents the Human clone 23933 mRNA (B) Genes that are upregulated in α6+/MHCI+ cells (TA cells), and subsequently downregulated in suprabasal cells.
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Figure 8: Changes in the gene expression during epidermal differentiation. (A) Genes that are gradually downregulated, or upregulated during epidermal differentiation. The EST* represents the Human clone 23933 mRNA (B) Genes that are upregulated in α6+/MHCI+ cells (TA cells), and subsequently downregulated in suprabasal cells.

Mentions: To gain further insights of epidermal differentiation, we compared our database with the published database of differentially expressed genes in basal and suprabasal layers of the human epidermis [60]. The comparison of our data with the transcriptional profile of the genes that are differentially expressed in the basal and differentiated layers of the epidermis suggests that TGF-β/phospho-Smad pathway-induced transcription profile fades along the epidermal differentiation axis. The abundance of transcripts, which are upregulated by TGF-β/phospho-Smad pathway (such as COL6A1, LTBP2, MMP9, PLAT), decrease during differentiation, from presumptive stem to transient amplifying cells (basal layer) and further to cells of the suprabasal layers, where these transcripts are present at the lowest level. In addition, the transcript of MADH3, a transcriptional activator of TGF-β responses, is also increasingly downregulated. Conversely, abundance of transcripts, which are downregulated by TGF-β/phospho-Smad pathway (such as KLF4 and MYC), appear to positively correlate with the increase of epidermal differentiation (Figure 8A).


Transcriptional profiling of putative human epithelial stem cells.

Koçer SS, Djurić PM, Bugallo MF, Simon SR, Matic M - BMC Genomics (2008)

Changes in the gene expression during epidermal differentiation. (A) Genes that are gradually downregulated, or upregulated during epidermal differentiation. The EST* represents the Human clone 23933 mRNA (B) Genes that are upregulated in α6+/MHCI+ cells (TA cells), and subsequently downregulated in suprabasal cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2536675&req=5

Figure 8: Changes in the gene expression during epidermal differentiation. (A) Genes that are gradually downregulated, or upregulated during epidermal differentiation. The EST* represents the Human clone 23933 mRNA (B) Genes that are upregulated in α6+/MHCI+ cells (TA cells), and subsequently downregulated in suprabasal cells.
Mentions: To gain further insights of epidermal differentiation, we compared our database with the published database of differentially expressed genes in basal and suprabasal layers of the human epidermis [60]. The comparison of our data with the transcriptional profile of the genes that are differentially expressed in the basal and differentiated layers of the epidermis suggests that TGF-β/phospho-Smad pathway-induced transcription profile fades along the epidermal differentiation axis. The abundance of transcripts, which are upregulated by TGF-β/phospho-Smad pathway (such as COL6A1, LTBP2, MMP9, PLAT), decrease during differentiation, from presumptive stem to transient amplifying cells (basal layer) and further to cells of the suprabasal layers, where these transcripts are present at the lowest level. In addition, the transcript of MADH3, a transcriptional activator of TGF-β responses, is also increasingly downregulated. Conversely, abundance of transcripts, which are downregulated by TGF-β/phospho-Smad pathway (such as KLF4 and MYC), appear to positively correlate with the increase of epidermal differentiation (Figure 8A).

Bottom Line: This study demonstrates that alpha 6+/MHCI- cells have additional characteristics attributed to stem cells.Our study is important for understanding self renewal and differentiation of epidermal stem cells, and for elucidating signaling pathways involved in those processes.The generated data base may serve those working with other human epithelial tissue progenitors.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biochemistry and Cell Biology, State University of New York at Stony Brook, Stony Brook, NY, USA. Salih.Kocer@yale.edu

ABSTRACT

Background: Human interfollicular epidermis is sustained by the proliferation of stem cells and their progeny, transient amplifying cells. Molecular characterization of these two cell populations is essential for better understanding of self renewal, differentiation and mechanisms of skin pathogenesis. The purpose of this study was to obtain gene expression profiles of alpha 6+/MHCI+, transient amplifying cells and alpha 6+/MHCI-, putative stem cells, and to compare them with existing data bases of gene expression profiles of hair follicle stem cells. The expression of Major Histocompatibility Complex (MHC) class I, previously shown to be absent in stem cells in several tissues, and alpha 6 integrin were used to isolate MHCI positive basal cells, and MHCI low/negative basal cells.

Results: Transcriptional profiles of the two cell populations were determined and comparisons made with published data for hair follicle stem cell gene expression profiles. We demonstrate that presumptive interfollicular stem cells, alpha 6+/MHCI- cells, are enriched in messenger RNAs encoding surface receptors, cell adhesion molecules, extracellular matrix proteins, transcripts encoding members of IFN-alpha family proteins and components of IFN signaling, but contain lower levels of transcripts encoding proteins which take part in energy metabolism, cell cycle, ribosome biosynthesis, splicing, protein translation, degradation, DNA replication, repair, and chromosome remodeling. Furthermore, our data indicate that the cell signaling pathways Notch1 and NF-kappaB are downregulated/inhibited in MHC negative basal cells.

Conclusion: This study demonstrates that alpha 6+/MHCI- cells have additional characteristics attributed to stem cells. Moreover, the transcription profile of alpha 6+/MHCI- cells shows similarities to transcription profiles of mouse hair follicle bulge cells known to be enriched for stem cells. Collectively, our data suggests that alpha 6+/MHCI- cells may be enriched for stem cells. This study is the first comprehensive gene expression profile of putative human epithelial stem cells and their progeny that were isolated directly from neonatal foreskin tissue. Our study is important for understanding self renewal and differentiation of epidermal stem cells, and for elucidating signaling pathways involved in those processes. The generated data base may serve those working with other human epithelial tissue progenitors.

Show MeSH
Related in: MedlinePlus