BMP signaling: at the gate between activated melanocyte stem cells and differentiation.
BMP signaling: at the gate between activated melanocyte stem cells and differentiation.
复制标题
DOI：
10.1101/gad.340281.120
复制
发表时间：
2020-12-01
影响因子：
10.5
通讯作者：
Fuchs E
中科院分区：
文献类型：
--
作者：
Infarinato NR;Stewart KS;Yang Y;Gomez NC;Pasolli HA;Hidalgo L;Polak L;Carroll TS;Fuchs E
在这里，Reinato等人研究了调节静止黑素细胞干细胞（McSC）活化以产生增殖后代的信号传导因子，所述增殖后代分化成产生色素的黑素细胞。在小鼠中使用条件性谱系特异性遗传消融研究，他们发现谱系中BMP信号传导的丧失导致黑素细胞成熟受阻导致毛发变灰，并且进一步表明，在WNT介导的McSCs激活后，BMP和WNT通路通过促进LEF1和MITF依赖性分化来协同触发增殖后代的定型。通过与毛发周期同步的反复发作，静止的黑素细胞干细胞（McSC）被激活以产生增殖的后代，所述后代分化成产生色素的黑素细胞。协调这些事件的信号因素仍然不完全清楚。在这里，我们使用单细胞RNA测序与比较基因表达分析，以阐明通过静止，激活和黑素细胞成熟的McSCs的转录动力学。随着WNT和BMP信号的增加，我们发现了沿着这一进程的会聚迹象，我们希望了解这些通路是如何整合的。通过对小鼠进行条件性谱系特异性基因消融研究，我们发现谱系中BMP信号的丧失会导致黑素细胞成熟受阻而导致头发变白。有趣的是，我们发现BMP信号在激活的McSCs下游起作用，并维持WNT效应子，转录因子LEF1。采用伪时间分析，遗传学和染色质美化，我们表明，以下WNT介导的激活的McSCs，BMP和WNT通路合作，以触发承诺的增殖后代通过燃料LEF1和MITF依赖性分化。我们的研究结果揭示了毛囊中黑素细胞谱系进展的信号相互作用和时间线索，并强调了BMP信号在驱动完全分化中的关键作用。
Here, Infarinato et al. investigated the signaling factors regulating activation of quiescent melanocyte stem cells (McSCs) to generate proliferative progeny that differentiate into pigment-producing melanocytes. Using conditional lineage-specific genetic ablation studies in mice, they found that loss of BMP signaling in the lineage leads to hair graying due to a block in melanocyte maturation, and furthermore show that following WNT-mediated activation of McSCs, BMP, and WNT pathways collaborate to trigger the commitment of proliferative progeny by fueling LEF1- and MITF-dependent differentiation. Through recurrent bouts synchronous with the hair cycle, quiescent melanocyte stem cells (McSCs) become activated to generate proliferative progeny that differentiate into pigment-producing melanocytes. The signaling factors orchestrating these events remain incompletely understood. Here, we use single-cell RNA sequencing with comparative gene expression analysis to elucidate the transcriptional dynamics of McSCs through quiescence, activation, and melanocyte maturation. Unearthing converging signs of increased WNT and BMP signaling along this progression, we endeavored to understand how these pathways are integrated. Employing conditional lineage-specific genetic ablation studies in mice, we found that loss of BMP signaling in the lineage leads to hair graying due to a block in melanocyte maturation. We show that interestingly, BMP signaling functions downstream from activated McSCs and maintains WNT effector, transcription factor LEF1. Employing pseudotime analysis, genetics, and chromatin landscaping, we show that following WNT-mediated activation of McSCs, BMP and WNT pathways collaborate to trigger the commitment of proliferative progeny by fueling LEF1- and MITF-dependent differentiation. Our findings shed light upon the signaling interplay and timing of cues that orchestrate melanocyte lineage progression in the hair follicle and underscore a key role for BMP signaling in driving complete differentiation.
登录
查看更多内容
影响因子：
64.8
作者：
Cao, Junyue;Spielmann, Malte;Shendure, Jay
通讯作者：
Shendure, Jay
影响因子：
46.9
作者：
Becht, Etienne;McInnes, Leland;Newell, Evan W.
通讯作者：
Newell, Evan W.
影响因子：
23.9
作者：
Adam RC;Yang H;Ge Y;Lien WH;Wang P;Zhao Y;Polak L;Levorse J;Baksh SC;Zheng D;Fuchs E
通讯作者：
Fuchs E
影响因子：
64.8
作者：
Chang, Chiung-Ying;Pasolli, H. Amalia;Giannopoulou, Eugenia G.;Guasch, Geraldine;Gronostajski, Richard M.;Elemento, Olivier;Fuchs, Elaine
通讯作者：
Fuchs, Elaine
影响因子：
64.5
作者：
Hsu YC;Pasolli HA;Fuchs E
通讯作者：
Fuchs E