Neural crest cells retain their capability for multipotential differentiation even after lineage‐restricted stages

Motohashi, Tsutomu; Yamanaka, Katsumasa; Chiba, Kairi; Miyajima, Kentaro; Aoki, Hitomi; Hirobe, Tomohisa; Kunisada, Takahiro

doi:10.1002/dvdy.22658

Cited by 21 publications

(30 citation statements)

References 45 publications

(65 reference statements)

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“…Both types of cells were shown to differentiate into neurons, glial cells, and melanocytes. These results support the concept that NCCs maintain their multipotency even after emerging from the neural tube regardless of their migratory pathways (Motohashi et al, ).…”

Section: Introductionsupporting

confidence: 88%

The stemness of neural crest cells and their derivatives

Kunisada

Tezulka

Aoki

et al. 2014

Birth Defects Research Pt C

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Neural crest cells (NCCs) are unique to vertebrates and emerge from the border of the neural plate and subsequently migrate extensively throughout the embryo after which they differentiate into many types of cells. This multipotency is the main reason why NCCs are regarded as a versatile tool for stem cell biology and have been gathering attention for their potential use in stem cell based therapy. Multiple sets of networks comprised of signaling molecules and transcription factors regulate every developmental phase of NCCs, including maintenance of their multipotency. Pluripotent stem cell lines, such as embryonic stem cells and induced pluripotent stem (iPS) cells, facilitate the induction of NCCs in combination with sophisticated culture systems used for neural stem cells, although at present, clinical experiments for NCC-based cell therapy need to be improved. Unexpectedly, the multipotency of NCCs is maintained after they reach the target tissues as tissue neural crest stem cells (NCSCs) that may contribute to the establishment of NCC-derived multipotential stem cells. In addition, under specific culture conditions, fate-restricted unipotent descendants of NCCs, such as melanoblasts, show multipotency to differentiate into melanocytes, neurons, and glia cells. These properties contribute to the additional versatility of NCCs for therapeutic application and to better understand NCC development.

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Section: Introductionsupporting

confidence: 88%

The stemness of neural crest cells and their derivatives

Kunisada

Tezulka

Aoki

et al. 2014

Birth Defects Research Pt C

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“…1A); P2, P6, P14, adult anagen III/IV (7dpp) and adult catagen VII (21 days post plucking, 21dpp). Despite the availability of a number of useful fluorescent Sox10 reporter mice [26]–[28], we opted to characterize protein expression with immunolabeling as this method is applicable to non-transgenic mouse studies. Using antibodies, we observed that nearly all DCT + cells within hairs co-express SOX10 regardless of time point, location or differentiation status (Fig.…”

Section: Resultsmentioning

confidence: 99%

A Dual Role for SOX10 in the Maintenance of the Postnatal Melanocyte Lineage and the Differentiation of Melanocyte Stem Cell Progenitors

et al. 2013

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During embryogenesis, the transcription factor, Sox10, drives the survival and differentiation of the melanocyte lineage. However, the role that Sox10 plays in postnatal melanocytes is not established. We show in vivo that melanocyte stem cells (McSCs) and more differentiated melanocytes express SOX10 but that McSCs remain undifferentiated. Sox10 knockout (Sox10fl; Tg(Tyr::CreER)) results in loss of both McSCs and differentiated melanocytes, while overexpression of Sox10 (Tg(DctSox10)) causes premature differentiation and loss of McSCs, leading to hair graying. This suggests that levels of SOX10 are key to normal McSC function and Sox10 must be downregulated for McSC establishment and maintenance. We examined whether the mechanism of Tg(DctSox10) hair graying is through increased expression of Mitf, a target of SOX10, by asking if haploinsufficiency for Mitf (Mitfvga9) can rescue hair graying in Tg(DctSox10) animals. Surprisingly, Mitfvga9 does not mitigate but exacerbates Tg(DctSox10) hair graying suggesting that MITF participates in the negative regulation of Sox10 in McSCs. These observations demonstrate that while SOX10 is necessary to maintain the postnatal melanocyte lineage it is simultaneously prevented from driving differentiation in the McSCs. This data illustrates how tissue-specific stem cells can arise from lineage-specified precursors through the regulation of the very transcription factors important in defining that lineage.

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“…Whether MBs fundamentally possess the multipotency or monopotent MBs are induced to become multipotent by their surroundings is presently unknown. We previously showed that the multipotency of NCCs was retained just after delaminating from the neural tubes and after migrating to their targeting tissues (Motohashi et al, ). This finding suggests that the multipotency of NCC is continuously retained in their derivatives, allowing us to speculate that the multipotency of MBs is an intrinsic character.…”

Section: Discussionmentioning

confidence: 99%

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

Watanabe

Motohashi

Nishioka

et al. 2016

Developmental Dynamics

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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,

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Neural crest cells retain their capability for multipotential differentiation even after lineage‐restricted stages

Cited by 21 publications

References 45 publications

The stemness of neural crest cells and their derivatives

The stemness of neural crest cells and their derivatives

A Dual Role for SOX10 in the Maintenance of the Postnatal Melanocyte Lineage and the Differentiation of Melanocyte Stem Cell Progenitors

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

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