@article{e3852ee2e339473b9c384b2bf274a761,
title = "Apical-basal polarity precisely determines intestinal stem cell number by regulating Prospero threshold",
abstract = "Apical-basal polarity and cell-fate determinants are crucial for the cell fate and control of stem cell numbers. However, their interplay leading to a precise stem cell number remains unclear. Drosophila pupal intestinal stem cells (pISCs) asymmetrically divide, generating one apical ISC progenitor and one basal Prospero (Pros)+ enteroendocrine mother cell (EMC), followed by symmetric divisions of each daughter before adulthood, providing an ideal system to investigate the outcomes of polarity loss. Using lineage tracing and ex vivo live imaging, we identify an interlocked polarity regulation network precisely determining ISC number: Bazooka inhibits Pros accumulation by activating Notch signaling to maintain stem cell fate in pISC apical daughters. A threshold of Pros promotes differentiation to EMCs and avoids ISC-like cell fate, and over-threshold of Pros inhibits miranda expression to ensure symmetric divisions in pISC basal daughters. Our work suggests that a polarity-dependent threshold of a differentiation factor precisely controls stem cell number.",
keywords = "apical-basal polarity, aPKC, Baz, CP: Cell biology, CP: Stem cell research, Mira, Notch activation, Par-6, Pros threshold, pupal intestinal stem cell, stem cell number",
author = "Song Wu and Yang Yang and Ruizhi Tang and Song Zhang and Peizhong Qin and Rong Lin and Neus Rafel and Lucchetta, {Elena M.} and Benjamin Ohlstein and Zheng Guo",
note = "Funding Information: We thank Drs. H. Wang, J. Chen, Z. Zhai, H. Chen, Z. Wang, and Y. Hong for valuable comments; Drs. G. Struhl, C. Qoe, Y. Jan, F. Yu, H. Wang, Y. Song, Z. Zhai, BDSC, VDRC, DGRC, and Tsinghua Fly Center for fly strains; and Drs. J. Chen, X. Yang, F. Yu, H. Wang, and DSHB for antibodies. This work was supported by the National Natural Science Foundation of China ( 31970817 to Z.G., 31771625 to Z.G., 32271074 to Z.G., and 31900618 to S.W.) and China Postdoctoral Science Foundation grant 2017M622408 (to S.W.). Funding Information: We thank Drs. H. Wang, J. Chen, Z. Zhai, H. Chen, Z. Wang, and Y. Hong for valuable comments; Drs. G. Struhl, C. Qoe, Y. Jan, F. Yu, H. Wang, Y. Song, Z. Zhai, BDSC, VDRC, DGRC, and Tsinghua Fly Center for fly strains; and Drs. J. Chen, X. Yang, F. Yu, H. Wang, and DSHB for antibodies. This work was supported by the National Natural Science Foundation of China (31970817 to Z.G. 31771625 to Z.G. 32271074 to Z.G. and 31900618 to S.W.) and China Postdoctoral Science Foundation grant 2017M622408 (to S.W.). Y.Y. S.W. R.T. and Z.G. conceptualized and designed experiments; Y.Y. S.W. R.T. S.Z. P.Q. and Z.G. performed experiments and interpreted data; S.W. B.O. and Z.G. wrote the manuscript; N.R. E.M.L. B.O. R.T. and Z.G. designed the ex vivo live-imaging method; R.T. performed pupal ex vivo live-imaging studies and data analysis; R.L. and Z.G. supplied resources and funding; Z.G. supervised the project, including study design, interpretation, and writing. The authors declare no competing interests. We support inclusive, diverse, and equitable conduct of research. Publisher Copyright: {\textcopyright} 2023 The Author(s)",
year = "2023",
month = feb,
day = "28",
doi = "10.1016/j.celrep.2023.112093",
language = "English (US)",
volume = "42",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "2",
}