title: Rac1 drives intestinal stem cell proliferation and regeneration.
abstract: Adult stem cells are responsible for maintaining the balance between cell proliferation and differentiation within self-renewing tissues. The molecular and cellular mechanisms mediating such balance are poorly understood. The production of reactive oxygen species (ROS) has emerged as an important mediator of stem cell homeostasis in various systems. Our recent work demonstrates that Rac1-dependent ROS production mediates intestinal stem cell (ISC) proliferation in mouse models of colorectal cancer (CRC). Here, we use the adult Drosophila midgut and the mouse small intestine to directly address the role of Rac1 in ISC proliferation and tissue regeneration in response to damage. Our results demonstrate that Rac1 is necessary and sufficient to drive ISC proliferation and regeneration in an ROS-dependent manner. Our data point to an evolutionarily conserved role of Rac1 in intestinal homeostasis and highlight the value of combining work in the mammalian and Drosophila intestine as paradigms to study stem cell biology.
authors: The Beatson Institute for Cancer Research; Glasgow, UK.
authors: Kevin B
authors: KB
authors: Myant
authors: Alessandro
authors: A
authors: Scopelliti
authors: Sara
authors: S
authors: Haque
authors: Marcos
authors: M
authors: Vidal
authors: Owen J
authors: OJ
authors: Sansom
authors: Julia B
authors: JB
authors: Cordero
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007422:Intestines / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism; D012038:Regeneration; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D017382:Reactive Oxygen Species; D020830:rac1 GTP-Binding Protein
keywords: Drosophila; ROS; Rac1; intestinal stem cells; mouse; regeneration
references: Genes Dev. 2009 Oct 1;23(19):2333-44
references: 19797770
references: Science. 2003 Oct 17;302(5644):459-62
references: 14564011
references: Cell Stem Cell. 2013 Jun 6;12(6):761-73
references: 23665120
references: Cell Stem Cell. 2008 Oct 9;3(4):442-55
references: 18940735
references: Brain Res. 2005 Apr 8;1040(1-2):137-50
references: 15804435
references: Biochim Biophys Acta. 2008 Oct;1780(10):1093-100
references: 18656526
references: Cell Stem Cell. 2007 Jun 7;1(1):101-12
references: 18371339
references: Clin Exp Metastasis. 2007;24(8):657-72
references: 18000759
references: EMBO J. 2012 Oct 3;31(19):3901-17
references: 22948071
references: Development. 1993 Jun;118(2):401-15
references: 8223268
references: Nature. 2006 Jan 26;439(7075):475-9
references: 16340959
references: Cell Stem Cell. 2011 Feb 4;8(2):188-99
references: 21295275
references: Cell Stem Cell. 2007 Aug 16;1(2):140-52
references: 18371346
references: Int J Mol Med. 2013 Mar;31(3):511-5
references: 23313933
references: Dev Cell. 2010 Aug 17;19(2):259-69
references: 20708588
references: Genesis. 2004 Jul;39(3):186-93
references: 15282745
references: Cell. 2009 Jun 26;137(7):1343-55
references: 19563763
references: Nature. 2004 Oct 21;431(7011):997-1002
references: 15496926
references: Cell Host Microbe. 2009 Feb 19;5(2):200-11
references: 19218090
references: Nature. 2006 Jan 26;439(7075):470-4
references: 16340960
references: Science. 2005 Mar 25;307(5717):1904-9
references: 15790842
references: Nature. 2009 Sep 24;461(7263):537-41
references: 19727075
references: Cell Stem Cell. 2009 Jan 9;4(1):49-61
references: 19128792