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DOI10.1073/pnas.2006786118
Mad dephosphorylation at the nuclear pore is essential for asymmetric stem cell division
Sardi J.; Bener M.B.; Simao T.; Descoteaux A.E.; Slepchenko B.M.; Inaba M.
发表日期2021
ISSN00278424
卷号118期号:13
英文摘要Stem cells divide asymmetrically to generate a stem cell and a differentiating daughter cell. Yet, it remains poorly understood how a stem cell and a differentiating daughter cell can receive distinct levels of niche signal and thus acquire different cell fates (self-renewal versus differentiation), despite being adjacent to each other and thus seemingly exposed to similar levels of niche signaling. In the Drosophila ovary, germline stem cells (GSCs) are maintained by short range bone morphogenetic protein (BMP) signaling; the BMP ligands activate a receptor that phosphorylates the downstream molecule mothers against decapentaplegic (Mad). Phosphorylated Mad (pMad) accumulates in the GSC nucleus and activates the stem cell transcription program. Here, we demonstrate that pMad is highly concentrated in the nucleus of the GSC, while it quickly decreases in the nucleus of the differentiating daughter cell, the precystoblast (preCB), before the completion of cytokinesis. We show that a known Mad phosphatase, Dullard (Dd), is required for the asymmetric partitioning of pMad. Our mathematical modeling recapitulates the high sensitivity of the ratio of pMad levels to the Mad phosphatase activity and explains how the asymmetry arises in a shared cytoplasm. Together, these studies reveal a mechanism for breaking the symmetry of daughter cells during asymmetric stem cell division. © 2021 National Academy of Sciences. All rights reserved.
英文关键词Asymmetric division; BMP signaling; Drosophila; Germline stem cells; Virtual Cell
语种英语
scopus关键词bone morphogenetic protein; DNA; ligand; Article; cell differentiation; cell division; cell fate; cell population; controlled study; cytokinesis; cytoplasm; daughter cell; DNA synthesis; Drosophila; germline stem cell; human; mathematical model; mouse; nonhuman; nuclear pore; priority journal; protein dephosphorylation; sensitivity analysis; stem cell
来源期刊Proceedings of the National Academy of Sciences of the United States of America
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/180074
作者单位Department of Cell Biology, University of Connecticut Health, Farmington, CT 06030, United States; Richard D. Berlin Center for Cell Analysis and Modeling, University of Connecticut Health, Farmington, CT 06030, United States
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Sardi J.,Bener M.B.,Simao T.,et al. Mad dephosphorylation at the nuclear pore is essential for asymmetric stem cell division[J],2021,118(13).
APA Sardi J.,Bener M.B.,Simao T.,Descoteaux A.E.,Slepchenko B.M.,&Inaba M..(2021).Mad dephosphorylation at the nuclear pore is essential for asymmetric stem cell division.Proceedings of the National Academy of Sciences of the United States of America,118(13).
MLA Sardi J.,et al."Mad dephosphorylation at the nuclear pore is essential for asymmetric stem cell division".Proceedings of the National Academy of Sciences of the United States of America 118.13(2021).
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