Multipotency of melanoblasts isolated from murine skin depends on the notch signal

Abstract

Background: Melanoblasts (MBs), derived from neural crest cells, only differentiate into melanocytes (Ms) in vivo. We previously showed that MBs isolated from mouse skin were multipotent, generating neurons (Ns) and glial cells (Gs) together with Ms. Using Sox10-IRES-Venus mice and mouse embryonic stem cells, we investigated how MBs expressed their multipotency. Results: MBs generated colonies containing Ns, Gs, and Ms in the presence of ST2 stromal cells, but they generated only M colonies when incubated with keratinocytes or ST2 culture supernatant, thus showing that MBs required contact with ST2 stromal cells for expression of their multipotency. Notch signaling was shown to be one of the important cues for the maintenance and differentiation of MBs through cell-cell contact. When Notch signaling was inhibited, MBs mainly generated colonies that contained just one type of cells, Ns, Gs, or Ms; the number of colonies containing two or three types of cells markedly decreased even on ST2 stromal cells, showing restriction of their differentiation potency. Whereas when Notch signaling was activated, the number of colonies containing two or three types of cells increased, indicating that their multipotency had been maintained. Conclusions: Our results demonstrate that Notch signaling played novel roles in MB multipotency. Developmental Dynamics 245:460-471,

Cell Fate Decisions in the Neural Crest, from Pigment Cell to Neural Development

“…Conversely, the identification of NCSCs, and their isolation from multiple locations throughout the body, indicated that at least some individual NCCs retained multipotency during migration and in their post-migratory locations (reviewed in [48]). Some of these cells, most notably those (Melanocyte Stem Cells) giving rise to melanocytes in the adult skin, were initially assumed to be unipotent, but further investigation in mammals showed they had latent multipotency [49,50]. This begs the question of whether these cells are somehow different from the beginning, or is it their final location (the niche) that enables them to retain a cryptic multipotency?…”

“…Although sharing the properties noted, these NCSCs show differences in their apparent fate biases, reflecting their source location (e.g., [97]). MSCs and NCSCs have been shown to be NC derived; MSCs are probably best thought of as another, perhaps highly specialized, type of NCSC, since they have been shown to be multipotent too [50].…”

Regulation of melanocyte stem cell behavior by the niche microenvironment

“…Melanocyte stem cells are usually kept in a quiescent state, but can be activated at the beginning of the anagen phase of the hair cycle (Nishimura, ). Using melanocyte tagging in several transgenic mouse systems, McSCs have been found to behave as committed melanocyte lineage cells in vivo (Nishimura et al., , ), but cultured McSCs from hair follicles can differentiate not only into melanocytes but also multiple other lineage cells, such as neurons, glial cells, and smooth muscle cells (Watanabe et al., ). This suggests that McSCs still maintain some intrinsic flexibility or susceptibility to cell reprogramming and that the bulge niches may be important for the committed differentiation to melanocytes.…”

Exosomes from dental pulp cells attenuate bone loss in mouse experimental periodontitis

“…ST2 mesenchymal cells were maintained in 10% FBS-RPMI 1640 (Sigma-Aldrich) supplemented with 5 × 10 −5 M 2-ME (Sigma Aldrich) and 100 IU/ml benzylpenicillin (Meiji). 30,31 Differentiation of osteoclastic cells was assessed in co-cultures of ST2 and bone marrow cells obtained from 9-week-old male C57BL6 mice. 32 For this purpose, ST2 cells were plated in RPMI containing the supplements described above at a density of 20 000 cells/cm 2 .…”