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Pluripotency reprogramming potential of dermal papilla cells and the role of Wnt signaling in dermal papilla cells during hair follicle morphogenesis.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Pluripotency reprogramming potential of dermal papilla cells and the role of Wnt signaling in dermal papilla cells during hair follicle morphogenesis./
Author:	Tsai, Su-Yi.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2011,
Description:	134 p.
Notes:	Source: Dissertations Abstracts International, Volume: 72-12, Section: B.
Contained By:	Dissertations Abstracts International72-12B.
Subject:	Cellular biology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3454031
ISBN:	9781124627243

Pluripotency reprogramming potential of dermal papilla cells and the role of Wnt signaling in dermal papilla cells during hair follicle morphogenesis.
Tsai, Su-Yi.

Pluripotency reprogramming potential of dermal papilla cells and the role of Wnt signaling in dermal papilla cells during hair follicle morphogenesis. - Ann Arbor : ProQuest Dissertations & Theses, 2011 - 134 p.

Source: Dissertations Abstracts International, Volume: 72-12, Section: B.

Thesis (Ph.D.)--Mount Sinai School of Medicine, 2011.

Reprogramming patient-specific somatic cells into induced pluripotent stem (iPS) cells has great potential to develop feasible regenerative therapies. Many different cell types have been reprogrammed, most conveniently even peripheral blood mononuclear cells. However, they typically require the enforced expression of several transcription factors, posing mutagenesis risks as exogenous genetic material. To reduce this risk, iPS cells were previously generated with Oct4 alone from rather inaccessible neural stem cells that endogenously express the remaining reprogramming factors, and very recently from fibroblasts with Oct4 alone in combination with additional epigenetic regulators. Here I exploit that dermal papilla (DP) cells from hair follicles in the skin express all but one reprogramming factors to show that these accessible cells can be reprogrammed into iPS cells with the single transcription factor Oct4 and without further manipulation. Reprogramming was already achieved after three weeks and with efficiencies similar to other cell types reprogrammed with four factors. DP-derived iPS cells are comparable to embryonic stem cells with respect to morphology, gene expression and pluripotency. I conclude that DP cells may represent a preferred cell type for reprogramming accessible cells with less manipulation and for ultimately establishing safe conditions in the future by replacing Oct4 with small molecules. In the second part of this thesis, I investigated the role of Wnt/a-catenin signaling in DP during hair follicle morphogenesis. By using a new DP-specific ablation system, Tbx18-Cre, to conditionally ablate β-catenin in DP, I found that knocking out β-catenin in DP leads to phenotypes in early hair morphogenesis. The knockout mice display fewer hair follicles, impaired whisker growth, thinner skin and shorter hair shafts of all hair types, but have no detriments in hair cell lineage differentiation and proliferation. This thesis provides the first evidence that β-catenin in DP is required for hair morphogenesis. To understand the molecular mechanisms of how DP β-catenin is involved in hair formation, I have identified several gene candidates that may be directly or indirectly involved in the Wnt/β-catenin signaling pathway in DP during hair formation. β-catenin is known to have dual functions in both gene regulation and cell adhesion. Based on the gene expression analysis and the adhesion marker staining I presented in this thesis, no significantly change in adhesion molecule expression or localization can be observed in knockout mice. Therefore, the phenotypes of DP-specific β-catenin knockout mice most likely result from the function of a-catenin in transcriptional regulation downstream of Wnt signaling pathway, rather than involving cell adhesion.

ISBN: 9781124627243Subjects--Topical Terms:

3172791
Cellular biology.
Subjects--Index Terms:

Dermal papilla

Pluripotency reprogramming potential of dermal papilla cells and the role of Wnt signaling in dermal papilla cells during hair follicle morphogenesis.
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520 $a Reprogramming patient-specific somatic cells into induced pluripotent stem (iPS) cells has great potential to develop feasible regenerative therapies. Many different cell types have been reprogrammed, most conveniently even peripheral blood mononuclear cells. However, they typically require the enforced expression of several transcription factors, posing mutagenesis risks as exogenous genetic material. To reduce this risk, iPS cells were previously generated with Oct4 alone from rather inaccessible neural stem cells that endogenously express the remaining reprogramming factors, and very recently from fibroblasts with Oct4 alone in combination with additional epigenetic regulators. Here I exploit that dermal papilla (DP) cells from hair follicles in the skin express all but one reprogramming factors to show that these accessible cells can be reprogrammed into iPS cells with the single transcription factor Oct4 and without further manipulation. Reprogramming was already achieved after three weeks and with efficiencies similar to other cell types reprogrammed with four factors. DP-derived iPS cells are comparable to embryonic stem cells with respect to morphology, gene expression and pluripotency. I conclude that DP cells may represent a preferred cell type for reprogramming accessible cells with less manipulation and for ultimately establishing safe conditions in the future by replacing Oct4 with small molecules. In the second part of this thesis, I investigated the role of Wnt/a-catenin signaling in DP during hair follicle morphogenesis. By using a new DP-specific ablation system, Tbx18-Cre, to conditionally ablate β-catenin in DP, I found that knocking out β-catenin in DP leads to phenotypes in early hair morphogenesis. The knockout mice display fewer hair follicles, impaired whisker growth, thinner skin and shorter hair shafts of all hair types, but have no detriments in hair cell lineage differentiation and proliferation. This thesis provides the first evidence that β-catenin in DP is required for hair morphogenesis. To understand the molecular mechanisms of how DP β-catenin is involved in hair formation, I have identified several gene candidates that may be directly or indirectly involved in the Wnt/β-catenin signaling pathway in DP during hair formation. β-catenin is known to have dual functions in both gene regulation and cell adhesion. Based on the gene expression analysis and the adhesion marker staining I presented in this thesis, no significantly change in adhesion molecule expression or localization can be observed in knockout mice. Therefore, the phenotypes of DP-specific β-catenin knockout mice most likely result from the function of a-catenin in transcriptional regulation downstream of Wnt signaling pathway, rather than involving cell adhesion.
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653 $a Skin
653 $a Stem cell niche
653 $a Wnt signaling
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