Single-cell analysis identifies TCF4 and ID3 as a molecular switch of mammary epithelial stem cell differentiation

It is well known that the expansion of the mammary epithelium during the ovarian cycles in female mammals is supported by the transient increase in mammary epithelial stem cells (MaSCs). However, dissecting the molecular mechanisms that govern MaSC function and differentiation is poorly understood d...

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Vydané v:bioRxiv
Hlavní autori: Koon-Kiu Yan, Nekritz, Erin, Ju, Bensheng, Dong, Xinran, Werner, Rachel, Alsina-Beauchamp, Dayanira, Rosencrance, Celeste, Mukhopadhyay, Partha, Pan, Qingfei, Gorbatenko, Andrej, Ding, Liang, Wang, Yanyan, Qian, Chenxi, Shi, Hao, Shaner, Bridget, Sivaraman Natarajan, Chi, Hongbo, Easton, John, Silva, Jose, Yu, Jiyang
Médium: Paper
Jazyk:English
Vydavateľské údaje: Cold Spring Harbor Cold Spring Harbor Laboratory Press 17.08.2020
Cold Spring Harbor Laboratory
Vydanie:1.1
Predmet:
Cell differentiation
Computer applications
Developmental Biology
Epithelial cells
Epithelium
Mammary gland
Molecular evolution
Molecular modelling
Stem cells
Transcription factors
ISSN:2692-8205, 2692-8205
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Popis
Shrnutí:It is well known that the expansion of the mammary epithelium during the ovarian cycles in female mammals is supported by the transient increase in mammary epithelial stem cells (MaSCs). However, dissecting the molecular mechanisms that govern MaSC function and differentiation is poorly understood due to the lack of standardized methods for their identification and isolation. The development of robust single-cell mRNA sequencing () technologies and the computational methods to analyze them provides us with novel tools to approach the challenge of studying MaSCs in a completely unbiased way without. Here, we have performed the largest scRNA-seq analysis of individual mammary epithelial cells (~70,000 cells). Our study identified a distinct cell population presenting molecular features of MaSCs. Importantly, further purification and additional in-depth single-cell analysis of these cells revealed that they are not a fully homogenous entity. Instead, we identified three subpopulations representing early stages of lineage commitment. By tracking their molecular evolution through single-cell network analysis we found that one of these subpopulations represents bipotent MaSCs from which luminal and basal lineages diverge. Importantly, we also confirmed the presence of these cells in human mammary glands. Finally, through expression and network analysis studies, we have uncovered transcription factors that are activated early during lineage commitment. These data identified E2-2 (Tcf4) and ID3 as a potential molecular switch of mammary epithelial stem cell differentiation. Competing Interest Statement The authors have declared no competing interest.
Bibliografia:SourceType-Working Papers-1
ObjectType-Working Paper/Pre-Print-1
content type line 50
Competing Interest Statement: The authors have declared no competing interest.
ISSN:2692-8205
2692-8205
DOI:10.1101/2020.08.16.249854