Neural crest–derived cells with stem cell features can be traced back to multiple lineages in the adult skin

Abstract

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.

RETRACTED ARTICLE: Mesenchymal stem cells and neural crest stem cells from adult bone marrow: characterization of their surprising similarities and differences

“…In such a model, the fate of NCC was mapped in vivo by mating ROSA26 Cre reporter (R26R) mice, expressing β-galactosidase upon Cre-mediated recombination, with mice expressing Cre recombinase under the control of the Wnt1 promoter. Using this transgenic model, Sieber-Blum and Grim demonstrated the presence of pluripotent neural crest-derived cells in adult hair follicles [4], Wong et al identified NCC in mouse adult skin [5] and Nagoshi et al isolated NCC from adult bone marrow [6]. Another mouse expressing the Cre recombinase under the control of the P0 promoter is also used in the same approach to map the NCC and, in the bone marrow, both Cre expressing mice have allowed to tag the same neural crest-derived cells [7][8][9].…”

Stage- and area-specific control of stem cells in the developing nervous system

“…BMP signaling alone, on the other hand, instructively drives eNCSCs into the autonomic lineage in vitro [21], while in vivo BMP signaling regulates proliferation, differentiation and survival of NC-derived cells in a lineage specific fashion [22][23][24]. Cells with NCSC-like features can also be found in various postmigratory target structures of the neural crest, like in the embryonic sciatic nerve [25], adult skin [26,27], gut [28], adult dorsal root ganglia (DRG), whisker pad, and bone marrow [29]. However, such late stage NCSCs (e.g.…”

The proliferating field of neural crest stem cells

“…However, in clear contrast to the SKPs identified by Toma and colleagues, cells of these skin-derived spheres expressed the NCSC markers Sox10 and p75 (Toma et al, 2001;Wong et al, 2006). Selfrenewal was demonstrated by maintenance of Sox10/p75 expression in most cells over several months of passages.…”

“…However, in recent years, several other types of stem cells, of unexpectedly broad potential, have also been identified in the skin. These cells have been labeled epidermal neural crest stem cells (EPI-NCSCs, formerly epidermal NCSCs or even eNCSCs) and SKin-derived Precursors (SKPs; Toma et al, 2001;Sieber-Blum et al, 2004;Wong et al, 2006). EPI-NCSCs were identified by noting large numbers of neural crest-derived cells in the facial and back skin of adult mouse and were isolated by microdissection from the bulge area of whisker follicles (Sieber-Blum et al, 2004).…”

“…A further type of NC-derived precursor capable of forming floating spheres was identified from mouse whisker skin and from both mouse and human adult trunk skin, and these have also been called SKPs (Wong et al, 2006). However, in clear contrast to the SKPs identified by Toma and colleagues, cells of these skin-derived spheres expressed the NCSC markers Sox10 and p75 (Toma et al, 2001;Wong et al, 2006).…”