The Osa-containing SWI/SNF chromatin-remodeling complex regulates stem cell commitment in the adult Drosophila intestine.
The proportion of stem cells versus differentiated progeny is well balanced to maintain tissue homeostasis, which in turn depends on the balance of the different signaling pathways involved in stem cell self-renewal versus lineage-specific differentiation. In a screen for genes that regulate cell lineage determination in the posterior midgut, we identified that the Osa-containing SWI/SNF (Brahma) chromatin-remodeling complex regulates Drosophila midgut homeostasis. Mutations in subunits of the Osa-containing complex result in intestinal stem cell (ISC) expansion as well as enteroendocrine (EE) cell reduction. We further demonstrated that Osa regulates ISC self-renewal and differentiation into enterocytes by elaborating Notch signaling, and ISC commitment to differentiation into EE cells by regulating the expression of Asense, an EE cell fate determinant. Our data uncover a unique mechanism whereby the commitment of stem cells to discrete lineages is coordinately regulated by chromatin-remodeling factors.
Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. zengx2@mail.nih.gov
Xiankun
X
Zeng
Xinhua
X
Lin
Steven X
SX
Hou
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology; D047369:Chromatin Immunoprecipitation; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism / Q000502:physiology*; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004330:Drosophila / Q000254:growth & development*; D029721:Drosophila Proteins / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D007422:Intestines / Q000166:cytology / Q000254:growth & development*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*
D002868:Chromosomal Proteins, Non-Histone; D017931:DNA Primers; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C497759:N protein, Drosophila; D009419:Nerve Tissue Proteins; D051880:Receptors, Notch; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors; C407353:ase protein, Drosophila; C117995:osa protein, Drosophila
Chromatin-remodeling factor; Differentiation; Drosophila; Intestinal stem cells; Osa; SWI/SNF; Self-renewal