FoxA transcription factor Fork head maintains the intestinal stem/progenitor cell identities in Drosophila.

Autor: Lan Q; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States. Electronic address: ql17@alumni.utsw.edu., Cao M; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States., Kollipara RK; Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States., Rosa JB; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States., Kittler R; Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States., Jiang H; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States. Electronic address: Huaqi.Jiang@UTSouthwestern.edu.
Jazyk: angličtina
Zdroj: Developmental biology [Dev Biol] 2018 Jan 15; Vol. 433 (2), pp. 324-343. Date of Electronic Publication: 2017 Nov 03.
DOI: 10.1016/j.ydbio.2017.09.002
Abstrakt: Understanding how somatic stem cells respond to tissue needs is important, since aberrant somatic stem cell behaviors may lead to tissue degeneration or tumorigenesis. Here, from an in vivo RNAi screen targeting transcription factors that regulate intestinal regeneration, we uncovered a requirement for the Drosophila FoxA transcription factor Fork head (Fkh) in the maintenance of intestinal stem/progenitor cell identities. FoxA/Fkh maintains the expressions of stem/progenitor cell markers and is required for stem cell proliferation during intestinal homeostasis and regeneration. Furthermore, FoxA/Fkh prevents the intestinal stem/progenitor cells from precocious differentiation into the Enterocyte lineage, likely in cooperation with the transcription factor bHLH/Daughterless (Da). In addition, loss of FoxA/Fkh suppresses the intestinal tumorigenesis caused by Notch pathway inactivation. To reveal the gene program underlying stem/progenitor cell identities, we profiled the genome-wide chromatin binding sites of transcription factors Fkh and Da, and interestingly, around half of Fkh binding regions are shared by Da, further suggesting their collaborative roles. Finally, we identified the genes associated with their shared binding regions. This comprehensive gene list may contain stem/progenitor maintenance factors functioning downstream of Fkh and Da, and would be helpful for future gene discoveries in the Drosophila intestinal stem cell lineage.
(Copyright © 2017 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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