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CD133 expression correlates with membrane beta-catenin and E-cadherin loss from human hair follicle placodes during morphogenesis.

Gay DL, Yang CC, Plikus MV, Ito M, Rivera C, Treffeisen E, Doherty L, Spata M, Millar SE, Cotsarelis G - J. Invest. Dermatol. (2014)

Bottom Line: CD133 associates with membrane beta-catenin in early placodes, and its continued expression correlates with loss of beta-catenin and E-cadherin from the cell membrane at a time when E-cadherin transcriptional repressors Snail and Slug are not implicated.Stabilization of CD133 via anti-CD133 antibody treatment of human fetal scalp explants depresses beta-catenin and E-cadherin membrane localization.We discuss this unique correlation and suggest a hypothetical model whereby CD133 promotes morphogenesis in early hair follicle placodes through the localized removal of membrane beta-catenin proteins and subsequent AJ dissolution.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

ABSTRACT
Genetic studies suggest that the major events of human hair follicle development are similar to those in mice, but detailed analyses of this process are lacking. In mice, hair follicle placode "budding" is initiated by invagination of Wnt-induced epithelium into the underlying mesenchyme. Modification of adherens junctions (AJs) is clearly required for budding. Snail-mediated downregulation of AJ component E-cadherin is important for placode budding in mice. Beta-catenin, another AJ component, has been more difficult to study owing to its essential functions in Wnt signaling, a prerequisite for hair follicle placode induction. Here, we show that a subset of human invaginating hair placode cells expresses the stem cell marker CD133 during early morphogenesis. CD133 associates with membrane beta-catenin in early placodes, and its continued expression correlates with loss of beta-catenin and E-cadherin from the cell membrane at a time when E-cadherin transcriptional repressors Snail and Slug are not implicated. Stabilization of CD133 via anti-CD133 antibody treatment of human fetal scalp explants depresses beta-catenin and E-cadherin membrane localization. We discuss this unique correlation and suggest a hypothetical model whereby CD133 promotes morphogenesis in early hair follicle placodes through the localized removal of membrane beta-catenin proteins and subsequent AJ dissolution.

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Related in: MedlinePlus

CD133+ cells express genes indicative of early hair follicle placode morphogenesis and EMT(a) Representative dot plot of 13 week fetal scalp epidermal populations. Squares define regions of ITGA6+ and CD133+ sorted populations. (b) Venn diagram comparing overlap of gene expression in ITGA6+ and CD133+ populations. (c) Heatmap comparing differentially expressed genes in ITGA6+ and CD133+ populations from two independent array analyses. Green denotes upregulated and pink downregulated genes. N and N(t) = 2 arrays from 2 independent sorts. Results represent merged analyses (d) QPCR analyses comparing transcription levels of specific genes in sorted ITGA6+ (black bars) and CD133+ (gray bars) populations as described in Gay et al, 2013. N and N(t) = 3.
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Figure 3: CD133+ cells express genes indicative of early hair follicle placode morphogenesis and EMT(a) Representative dot plot of 13 week fetal scalp epidermal populations. Squares define regions of ITGA6+ and CD133+ sorted populations. (b) Venn diagram comparing overlap of gene expression in ITGA6+ and CD133+ populations. (c) Heatmap comparing differentially expressed genes in ITGA6+ and CD133+ populations from two independent array analyses. Green denotes upregulated and pink downregulated genes. N and N(t) = 2 arrays from 2 independent sorts. Results represent merged analyses (d) QPCR analyses comparing transcription levels of specific genes in sorted ITGA6+ (black bars) and CD133+ (gray bars) populations as described in Gay et al, 2013. N and N(t) = 3.

Mentions: To better define the role of CD133+ cells in placode development, 13 week fetal scalp epidermal cells were sorted for expression of CD133 and alpha6-integrin (Fig. 3a) and RNA subjected to microarray analyses. As expected, alpha6-integrin+CD133− (ITGA6+) and α6-integrin+CD133+ double positive (CD133+) populations, both of epidermal basal origin, shared expression of many genes (Fig. 3b Venn diagram). Fig. 3c shows a heatmap comparing differences in gene expression by ITGA6+ and CD133+ populations.


CD133 expression correlates with membrane beta-catenin and E-cadherin loss from human hair follicle placodes during morphogenesis.

Gay DL, Yang CC, Plikus MV, Ito M, Rivera C, Treffeisen E, Doherty L, Spata M, Millar SE, Cotsarelis G - J. Invest. Dermatol. (2014)

CD133+ cells express genes indicative of early hair follicle placode morphogenesis and EMT(a) Representative dot plot of 13 week fetal scalp epidermal populations. Squares define regions of ITGA6+ and CD133+ sorted populations. (b) Venn diagram comparing overlap of gene expression in ITGA6+ and CD133+ populations. (c) Heatmap comparing differentially expressed genes in ITGA6+ and CD133+ populations from two independent array analyses. Green denotes upregulated and pink downregulated genes. N and N(t) = 2 arrays from 2 independent sorts. Results represent merged analyses (d) QPCR analyses comparing transcription levels of specific genes in sorted ITGA6+ (black bars) and CD133+ (gray bars) populations as described in Gay et al, 2013. N and N(t) = 3.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4465595&req=5

Figure 3: CD133+ cells express genes indicative of early hair follicle placode morphogenesis and EMT(a) Representative dot plot of 13 week fetal scalp epidermal populations. Squares define regions of ITGA6+ and CD133+ sorted populations. (b) Venn diagram comparing overlap of gene expression in ITGA6+ and CD133+ populations. (c) Heatmap comparing differentially expressed genes in ITGA6+ and CD133+ populations from two independent array analyses. Green denotes upregulated and pink downregulated genes. N and N(t) = 2 arrays from 2 independent sorts. Results represent merged analyses (d) QPCR analyses comparing transcription levels of specific genes in sorted ITGA6+ (black bars) and CD133+ (gray bars) populations as described in Gay et al, 2013. N and N(t) = 3.
Mentions: To better define the role of CD133+ cells in placode development, 13 week fetal scalp epidermal cells were sorted for expression of CD133 and alpha6-integrin (Fig. 3a) and RNA subjected to microarray analyses. As expected, alpha6-integrin+CD133− (ITGA6+) and α6-integrin+CD133+ double positive (CD133+) populations, both of epidermal basal origin, shared expression of many genes (Fig. 3b Venn diagram). Fig. 3c shows a heatmap comparing differences in gene expression by ITGA6+ and CD133+ populations.

Bottom Line: CD133 associates with membrane beta-catenin in early placodes, and its continued expression correlates with loss of beta-catenin and E-cadherin from the cell membrane at a time when E-cadherin transcriptional repressors Snail and Slug are not implicated.Stabilization of CD133 via anti-CD133 antibody treatment of human fetal scalp explants depresses beta-catenin and E-cadherin membrane localization.We discuss this unique correlation and suggest a hypothetical model whereby CD133 promotes morphogenesis in early hair follicle placodes through the localized removal of membrane beta-catenin proteins and subsequent AJ dissolution.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

ABSTRACT
Genetic studies suggest that the major events of human hair follicle development are similar to those in mice, but detailed analyses of this process are lacking. In mice, hair follicle placode "budding" is initiated by invagination of Wnt-induced epithelium into the underlying mesenchyme. Modification of adherens junctions (AJs) is clearly required for budding. Snail-mediated downregulation of AJ component E-cadherin is important for placode budding in mice. Beta-catenin, another AJ component, has been more difficult to study owing to its essential functions in Wnt signaling, a prerequisite for hair follicle placode induction. Here, we show that a subset of human invaginating hair placode cells expresses the stem cell marker CD133 during early morphogenesis. CD133 associates with membrane beta-catenin in early placodes, and its continued expression correlates with loss of beta-catenin and E-cadherin from the cell membrane at a time when E-cadherin transcriptional repressors Snail and Slug are not implicated. Stabilization of CD133 via anti-CD133 antibody treatment of human fetal scalp explants depresses beta-catenin and E-cadherin membrane localization. We discuss this unique correlation and suggest a hypothetical model whereby CD133 promotes morphogenesis in early hair follicle placodes through the localized removal of membrane beta-catenin proteins and subsequent AJ dissolution.

Show MeSH
Related in: MedlinePlus