Gradual differentiation uncoupled from cell cycle exit generates heterogeneity in the epidermal stem cell layer.
Gradual differentiation uncoupled from cell cycle exit generates heterogeneity in the epidermal stem cell layer.
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DOI：
10.1038/s41556-022-01021-8
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发表时间：
2022-12
影响因子：
21.3
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中科院分区：
文献类型：
--
作者：
高度再生的组织不断产生终末分化的细胞来取代那些丢失的细胞。它们如何协调从未分化干细胞向有丝分裂后、分子上不同且通常空间上分离的分化群体的复杂过渡尚不清楚。在成人皮肤表皮中，干细胞室包含分子异质性亚群，其与分化的完整轨迹的关系仍然未知。在这里，我们表明，分化，从承诺退出干细胞层，是一个多天的过程中，细胞通过一个连续的转录变化与上调分化基因之前典型的干细胞基因下调过境。分化定向细胞仍然能够分裂以产生注定进一步分化的子细胞，表明分化与细胞周期退出解偶联。这些细胞分裂并不需要作为一个专性的过渡扩增程序的一部分，但有助于缓冲分化的细胞池在提高需求。因此，而不是不同的贡献，从多个祖细胞，一个连续的逐渐分化过程燃料稳态表皮营业额。Cockburn等报道，表皮分化是一个多天的过程，通过该过程，细胞经历独立于细胞周期退出而启动的连续的转录改变。
Highly regenerative tissues continuously produce terminally differentiated cells to replace those that are lost. How they orchestrate the complex transition from undifferentiated stem cells towards post-mitotic, molecularly distinct and often spatially segregated differentiated populations is not well understood. In the adult skin epidermis, the stem cell compartment contains molecularly heterogeneous subpopulations whose relationship to the complete trajectory of differentiation remains unknown. Here we show that differentiation, from commitment to exit from the stem cell layer, is a multi-day process wherein cells transit through a continuum of transcriptional changes with upregulation of differentiation genes preceding downregulation of typical stemness genes. Differentiation-committed cells remain capable of dividing to produce daughter cells fated to further differentiate, demonstrating that differentiation is uncoupled from cell cycle exit. These cell divisions are not required as part of an obligate transit-amplifying programme but help to buffer the differentiating cell pool during heightened demand. Thus, instead of distinct contributions from multiple progenitors, a continuous gradual differentiation process fuels homeostatic epidermal turnover. Cockburn et al. report that epidermal differentiation is a multi-day process through which cells undergo a continuum of transcriptional alterations initiated independently of cell cycle exit.
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影响因子：
23.9
作者：
Joost, Simon;Annusver, Karl;Kasper, Maria
通讯作者：
Kasper, Maria
影响因子：
30.8
作者：
Kim DS;Risca VI;Reynolds DL;Chappell J;Rubin AJ;Jung N;Donohue LKH;Lopez-Pajares V;Kathiria A;Shi M;Zhao Z;Deep H;Sharmin M;Rao D;Lin S;Chang HY;Snyder MP;Greenleaf WJ;Kundaje A;Khavari PA
通讯作者：
Khavari PA
影响因子：
11.8
作者：
Lee, Briana;Villarreal-Ponce, Alvaro;Fallahi, Magid;Ovadia, Jeremy;Sun, Peng;Yu, Qian-Chun;Ito, Seiji;Sinha, Satrajit;Nie, Qing;Dai, Xing
通讯作者：
Dai, Xing
影响因子：
21.3
作者：
Lopez, Rodolphe G.;Garcia-Silva, Susana;Nerlov, Claus
通讯作者：
Nerlov, Claus
影响因子：
3.9
作者：
Lavker, RM;Sun, TT
通讯作者：
Sun, TT