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Stem Cells Dev. 2019 Jul 15;28(14):944-953. doi: 10.1089/scd.2019.0011. Epub 2019 Jun 11.

TDP-43 is Required for Mammary Gland Repopulation and Proliferation of Mammary Epithelial Cells.

Zhao L1,2,3, Li L1,2, Xu H2,3, Ke H2, Zou L2, Yang Q2, Shen CJ4, Nie J5, Jiao B2,6,7.

Author information

1
1School of Life Sciences, University of Science and Technology of China, Hefei, China.
2
2State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
3
3Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, China.
4
4Institute of Molecular Biology, Academia Sinica, Nankang, Taipei, Taiwan.
5
5Department of Breast Cancer, Third Affiliated Hospital, Kunming Medical University, Kunming, China.
6
6KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
7
7Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, China.

Abstract

Mammary gland stem cells (MaSCs), assumed to be the original cells of breast cancer, play essential roles in regulating mammary gland homeostasis and development. Previously, we identified a crucial regulatory role of TAR DNA-binding protein 43 (TDP-43), an RNA-binding protein, in the progression of triple-negative breast cancer. However, the function of TDP-43 in MaSCs is unclear. Based on single-cell data analysis of the mammary gland, TDP-43 showed potential involvement in the regulation of MaSCs. We therefore investigated the effects of TDP-43 on the mammary gland development. Our data both in vitro and in vivo demonstrated that TDP-43 was required for the mammary gland repopulation, which suggested the potential role in the regulation of MaSCs. Knockdown of TDP-43 inhibited proliferation of mammary epithelial cells (MECs) and mammary morphogenesis. RNA-seq data and other experiments identified that loss of TDP-43 induced the upregulation of genes related to the cell cycle, providing a possible mechanism for TDP-43 in regulating mammary gland repopulation. Thus, our findings indicate a previously unknown role of TDP-43 in MECs.

KEYWORDS:

TDP-43; mammary gland repopulation; proliferation

PMID:
31062657
DOI:
10.1089/scd.2019.0011

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