TY - JOUR
T1 - FoxA transcription factor Fork head maintains the intestinal stem/progenitor cell identities in Drosophila
AU - Lan, Qing
AU - Cao, Min
AU - Kollipara, Rahul K.
AU - Rosa, Jeffrey B.
AU - Kittler, Ralf
AU - Jiang, Huaqi
N1 - Funding Information:
We thank R. PflanZ, X. Yang, VDRC and BDSC Stock Centers for reagents. The primary RNAi screen was performed in B. Edgar's lab at FHCRC with technical support from M. Glenley, MJ. Bravo and R. Blumhagen. We also thank V. Tran from X. Chen's lab for technical support. This work was supported by a NIH Grant to H. Jiang (NIDDK 102576 ).
Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2018/1/15
Y1 - 2018/1/15
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ydbio.2017.09.002
DO - 10.1016/j.ydbio.2017.09.002
M3 - Article
C2 - 29108672
AN - SCOPUS:85032924970
SN - 0012-1606
VL - 433
SP - 324
EP - 343
JO - Developmental Biology
JF - Developmental Biology
IS - 2
ER -