Wong CE, Paratore C, Dours-Zimmermann MT, Rochat A, Pietri T, Suter U, Zimmermann DR, Dufour S, Thiery JP, Meijer D, Beermann F, Barrandon Y, Sommer LNeural crest-derived cells with stem cell features can be traced back to multiple lineages in the adult skin. J Cell Biol 175(6): 1005-1015

Department of Biology, Institute of Cell Biology, Swiss Federal Institute of Technology ETH Zurich, CH-8093 Zurich, Switzerland.
The Journal of Cell Biology (Impact Factor: 9.83). 01/2007; 175(6):1005-15. DOI: 10.1083/jcb.200606062
Source: PubMed


Given their accessibility, multipotent skin-derived cells might be useful for future cell replacement therapies. We describe the isolation of multipotent stem cell-like cells from the adult trunk skin of mice and humans that express the neural crest stem cell markers p75 and Sox10 and display extensive self-renewal capacity in sphere cultures. To determine the origin of these cells, we genetically mapped the fate of neural crest cells in face and trunk skin of mouse. In whisker follicles of the face, many mesenchymal structures are neural crest derived and appear to contain cells with sphere-forming potential. In the trunk skin, however, sphere-forming neural crest-derived cells are restricted to the glial and melanocyte lineages. Thus, self-renewing cells in the adult skin can be obtained from several neural crest derivatives, and these are of distinct nature in face and trunk skin. These findings are relevant for the design of therapeutic strategies because the potential of stem and progenitor cells in vivo likely depends on their nature and origin.

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    • "These characteristics are similar to those of skin BC derivatives (Figure 3E; Figure S3D) and led us to investigate whether some BC derivatives show stem cell-like properties. For this purpose, we performed floating sphere cultures from the back skin of Prss56 Cre/+ , R26 tdTom newborn mice (Biernaskie et al., 2006; Wong et al., 2006). Numerous floating spheres were observed after 7–10 days in culture and could be propagated for at least 11 passages (Figure 4A). "
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    ABSTRACT: While neurogenic stem cells have been identified in rodent and human skin, their manipulation and further characterization are hampered by a lack of specific markers. Here, we perform genetic tracing of the progeny of boundary cap (BC) cells, a neural-crest-derived cell population localized at peripheral nerve entry/exit points. We show that BC derivatives migrate along peripheral nerves to reach the skin, where they give rise to terminal glia associated with dermal nerve endings. Dermal BC derivatives also include cells that self-renew in sphere culture and have broad in vitro differentiation potential. Upon transplantation into adult mouse dorsal root ganglia, skin BC derivatives efficiently differentiate into various types of mature sensory neurons. Together, this work establishes the embryonic origin, pathway of migration, and in vivo neurogenic potential of a major component of skin stem-like cells. It provides genetic tools to study and manipulate this population of high interest for medical applications. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
    Full-text · Article · Jul 2015 · Stem Cell Reports
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    • "Compared with the in vivo stripped Descemet's membrane, the resultant cell shape remained hexagonal during the entire knockdown period (5 wk of weekly treatment after the first week of culture followed by withdrawal for 1 wk) for HCEC monolayers treated with scRNA or p120-Kaiso siRNAs (Fig. 6 A). The resultant cell density was also maintained at the in vivo level by p120-Kaiso siRNAs in MESCM, but was decreased, however, by scRNA after 6 wk of culturing (Fig. 6 B). 1 wk after withdrawal, the resultant HCEC monolayer retained the centric expression of acetylate--catenin (a marker of the basal body and the primary cilium; Blitzer et al., 2011), uniform cytoplasmic expression of -tubulin and p75NTR (of which the latter is considered a marker of neural crest cells; Wong et al., 2006), and junctional expression of p120, N-cadherin, -catenin, -catenin, Zona occludens protein 1 (ZO-1), Na-K-ATPase, and F-actin (all are markers of HCECs), without expression of LEF1 and S100A4 (both are markers of EMT; Zhu et al., 2012; Fig. 6 C). Such expression of HCEC markers was consistent with the in vivo expression pattern previously reported by us (Zhu et al., 2012, 2014). "
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    ABSTRACT: Currently there are limited treatment options for corneal blindness caused by dysfunctional corneal endothelial cells. The primary treatment involves transplantation of healthy donor human corneal endothelial cells, but a global shortage of donor corneas necessitates other options. Conventional tissue approaches for corneal endothelial cells are based on EDTA-trypsin treatment and run the risk of irreversible endothelial mesenchymal transition by activating canonical Wingless-related integration site (Wnt) and TGF-β signaling. Herein, we demonstrate an alternative strategy that avoids disruption of cell-cell junctions and instead activates Ras homologue gene family A (RhoA)-Rho-associated protein kinase (ROCK)-canonical bone morphogenic protein signaling to reprogram adult human corneal endothelial cells to neural crest-like progenitors via activation of the miR302b-Oct4-Sox2-Nanog network. This approach allowed us to engineer eight human corneal endothelial monolayers of transplantable size, with a normal density and phenotype from one corneoscleral rim. Given that a similar signal network also exists in the retinal pigment epithelium, this partial reprogramming approach may have widespread relevance and potential for treating degenerative diseases.
    Full-text · Article · Sep 2014 · The Journal of Cell Biology
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    • "Whisker follicles are known to serve as a local reservoir of mast cell precursors as it was shown by others that the middle part of dissected whisker follicles is able to produce mast cells in culture when stimulated with the appropriate growth and differentiation factors (Kumamoto et al., 2003). In addition, whisker follicle mesenchymal stem cells, like the cranial neural crest cells from which they are derived, can differentiate into adipocytes in vitro (Wong et al., 2006; Billon et al., 2008). "
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    ABSTRACT: Whisker follicles have multiple stem cell niches, including epidermal stem cells in the bulge as well as neural crest-derived stem cells and mast cell progenitors in the trabecular region. The neural crest-derived stem cells are a pool of melanocyte precursors. Previously, we found that the extracellular matrix glycoproteins tenascin-C and tenascin-W are expressed near CD34-positive cells in the trabecular stem cell niche of mouse whisker follicles. Here, we analyzed whiskers from tenascin-C knockout mice and found intrafollicular adipocytes and supernumerary mast cells. As Wnt/β-catenin signaling promotes melanogenesis and suppresses the differentiation of adipocytes and mast cells, we analyzed β-catenin subcellular localization in the trabecular niche. We found cytoplasmic and nuclear β-catenin in wild-type mice reflecting active Wnt/β-catenin signaling, whereas β-catenin in tenascin-C knockout mice was mostly cell membrane-associated and thus transcriptionally inactive. Furthermore, cells expressing the Wnt/β-catenin target gene cyclin D1 were enriched in the CD34-positive niches of wild-type compared to tenascin-C knockout mice. We then tested the effects of tenascins on this signaling pathway. We found that tenascin-C and tenascin-W can be co-precipitated with Wnt3a. In vitro, substrate bound tenascins promoted β-catenin-mediated transcription in the presence of Wnt3a, presumably due to the sequestration and concentration of Wnt3a near the cell surface. We conclude that the presence of tenascin-C in whiskers assures active Wnt/β-catenin signaling in the niche thereby maintaining the stem cell pool and suppressing aberrant differentiation, while in the knockout mice with reduced Wnt/β-catenin signaling, stem cells from the trabecular niche can differentiate into ectopic adipocytes and mast cells.
    Full-text · Article · Sep 2014 · Matrix Biology
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