Dermal papilla-induced hair differentiation of adult epithelial stem cells from human skin

The epithelial-mesenchymal interactions between keratinocyte stem cells and dermal papilla (DP) cells are crucial for normal development of the hair follicle as well as during hair cycling. During the cyclical regrowth of a new lower follicle, the multipotent hair follicle stem cells are stimulated to proliferate and differentiate through interactions with the underlying mesenchymal DP cells. To characterize the events occurring during the process of epithelial stem cell fate determination, we utilized a coculture system by incubating human hair follicle keratinocyte stem cells with DP cells. Using GeneChip microarrays, we analyzed changes in gene expression within the stem cells upon coculture with the DP over a 5-day time course. A number of important signaling pathways and growth factors were regulated. The hair-specific keratin 6hf (K6hf) gene proved a particularly good marker of hair differentiation, with a 7.9-fold increase in mRNA and resulting increased protein levels. The high expression of K6hf was unique to DP-induced keratinocyte differentiation, since expression of K6hf was not induced by high calcium. Since the β-catenin signaling pathway has been implicated in hair follicle development, we examined the role of β-catenin in our system and demonstrated that β-catenin/lef-1 signaling is required for DP-induced hair differentiation.

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Hair Follicle Dermal Cells Support Expansion of Murine and Human Embryonic and Induced Pluripotent Stem Cells and Promote Haematopoiesis in Mouse Cultures

Stem Cells International ◽

10.1155/2018/8631432 ◽

2018 ◽

Vol 2018 ◽

pp. 1-14

Author(s):

Jun Liu ◽

Claire A. Higgins ◽

Jenna C. Whitehouse ◽

Susan J. Harris ◽

Heather Crawford ◽

...

Keyword(s):

Stem Cells ◽

Induced Pluripotent Stem Cells ◽

Hair Follicle ◽

Pluripotent Stem Cells ◽

Embryonic Stem ◽

Dermal Papilla ◽

Epithelial Stem Cells ◽

Stem Cell Maintenance ◽

Induced Pluripotent ◽

Dermal Cells

In the hair follicle, the dermal papilla (DP) and dermal sheath (DS) support and maintain proliferation and differentiation of the epithelial stem cells that produce the hair fibre. In view of their regulatory properties, in this study, we investigated the interaction between hair follicle dermal cells (DP and DS) and embryonic stem cells (ESCs); induced pluripotent stem cells (iPSCs); and haematopoietic stem cells. We found that coculture of follicular dermal cells with ESCs or iPSCs supported their prolonged maintenance in an apparently undifferentiated state as established by differentiation assays, immunocytochemistry, and RT-PCR for markers of undifferentiated ESCs. We further showed that cytokines that are involved in ESC support are also expressed by cultured follicle dermal cells, providing a possible explanation for maintenance of ES cell stemness in cocultures. The same cytokines were expressed within folliclesin situin a pattern more consistent with a role in follicle growth activities than stem cell maintenance. Finally, we show that cultured mouse follicle dermal cells provide good stromal support for haematopoiesis in an established coculture model. Human follicular dermal cells represent an accessible and readily propagated source of feeder cells for pluripotent and haematopoietic cells and have potential for use in clinical applications.

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Faculty Opinions recommendation of Hair follicle dermal stem cells regenerate the dermal sheath, repopulate the dermal papilla, and modulate hair type.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725255220.793505555 ◽

2015 ◽

Author(s):

Jiro Kishimoto

Keyword(s):

Stem Cells ◽

Hair Follicle ◽

Dermal Papilla ◽

Hair Type

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Hair Follicle Epithelial Stem Cells Get Their Sox On

Cell Stem Cell ◽

10.1016/j.stem.2008.06.014 ◽

2008 ◽

Vol 3 (1) ◽

pp. 3-4 ◽

Cited By ~ 3

Author(s):

Angela M. Christiano

Keyword(s):

Stem Cells ◽

Hair Follicle ◽

Epithelial Stem Cells

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Preclinical evidence that the PPAR γ modulator, N ‐Acetyl‐ GED ‐0507‐34‐Levo, may protect human hair follicle epithelial stem cells against lichen planopilaris‐associated damage

Journal of the European Academy of Dermatology and Venereology ◽

10.1111/jdv.16114 ◽

2020 ◽

Vol 34 (4) ◽

Author(s):

J. Chéret ◽

I. Piccini ◽

J. Hardman‐Smart ◽

S. Ghatak ◽

M. Alam ◽

...

Keyword(s):

Stem Cells ◽

Hair Follicle ◽

Human Hair ◽

Epithelial Stem Cells ◽

Human Hair Follicle ◽

Lichen Planopilaris ◽

Ppar Γ

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Transcriptional Regulation of Dental Epithelial Cell Fate

International Journal of Molecular Sciences ◽

10.3390/ijms21238952 ◽

2020 ◽

Vol 21 (23) ◽

pp. 8952

Author(s):

Keigo Yoshizaki ◽

Satoshi Fukumoto ◽

Daniel D. Bikle ◽

Yuko Oda

Keyword(s):

Stem Cells ◽

Cell Fate ◽

Gene Mutations ◽

Dental Enamel ◽

The Body ◽

Epithelial Stem Cells ◽

Cell Fates ◽

Chromatin Regulators ◽

Dental Epithelium ◽

Potential Tool

Dental enamel is hardest tissue in the body and is produced by dental epithelial cells residing in the tooth. Their cell fates are tightly controlled by transcriptional programs that are facilitated by fate determining transcription factors and chromatin regulators. Understanding the transcriptional program controlling dental cell fate is critical for our efforts to build and repair teeth. In this review, we describe the current understanding of these regulators essential for regeneration of dental epithelial stem cells and progeny, which are identified through transgenic mouse models. We first describe the development and morphogenesis of mouse dental epithelium in which different subpopulations of epithelia such as ameloblasts contribute to enamel formation. Then, we describe the function of critical factors in stem cells or progeny to drive enamel lineages. We also show that gene mutations of these factors are associated with dental anomalies in craniofacial diseases in humans. We also describe the function of the master regulators to govern dental lineages, in which the genetic removal of each factor switches dental cell fate to that generating hair. The distinct and related mechanisms responsible for the lineage plasticity are discussed. This knowledge will lead us to develop a potential tool for bioengineering new teeth.

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Androgens downregulate BMP2 impairing the inductive role of dermal papilla cells on hair follicle stem cells differentiation

Molecular and Cellular Endocrinology ◽

10.1016/j.mce.2020.111096 ◽

2021 ◽

Vol 520 ◽

pp. 111096

Author(s):

Julieta María Ceruti ◽

Florencia Maia Oppenheimer ◽

Gustavo José Leirós ◽

María Eugenia Balañá

Keyword(s):

Stem Cells ◽

Hair Follicle ◽

Dermal Papilla ◽

Dermal Papilla Cells ◽

Hair Follicle Stem Cells ◽

Follicle Stem Cells

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Noncanonical NOTCH Signaling Limits Self-Renewal of Human Epithelial and Induced Pluripotent Stem Cells through ROCK Activation

Molecular and Cellular Biology ◽

10.1128/mcb.00577-13 ◽

2013 ◽

Vol 33 (22) ◽

pp. 4434-4447 ◽

Cited By ~ 31

Author(s):

Takashi Yugawa ◽

Koichiro Nishino ◽

Shin-ichi Ohno ◽

Tomomi Nakahara ◽

Masatoshi Fujita ◽

...

Keyword(s):

Stem Cells ◽

Induced Pluripotent Stem Cells ◽

Cell Fate ◽

Pluripotent Stem Cells ◽

Human Keratinocytes ◽

Small Gtpase ◽

Keratinocyte Differentiation ◽

Growth Defect ◽

Self Renewal ◽

Induced Pluripotent

NOTCH plays essential roles in cell fate specification during embryonic development and in adult tissue maintenance. In keratinocytes, it is a key inducer of differentiation. ROCK, an effector of the small GTPase Rho, is also implicated in keratinocyte differentiation, and its inhibition efficiently potentiates immortalization of human keratinocytes and greatly improves survival of dissociated human pluripotent stem cells. However, the molecular basis for ROCK activation is not fully established in these contexts. Here we provide evidence that intracellular forms of NOTCH1 trigger the immediate activation of ROCK1 independent of its transcriptional activity, promoting differentiation and resulting in decreased clonogenicity of normal human keratinocytes. Knockdown of NOTCH1 abrogated ROCK1 activation and conferred sustained clonogenicity upon differentiation stimuli. Treatment with a ROCK inhibitor, Y-27632, or ROCK1 silencing substantially rescued the growth defect induced by activated NOTCH1. Furthermore, we revealed that impaired self-renewal of human induced pluripotent stem cells upon dissociation is, at least in part, attributable to NOTCH-dependent ROCK activation. Thus, the present study unveils a novel NOTCH-ROCK pathway critical for cellular differentiation and loss of self-renewal capacity in a subset of immature cells.

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