Professor Fuchs has developed a strategy for purifying the population of adult mouse stem cells from their natural niche in the hair follicle. These cells undergo self-renewal, replenish hair follicles during cycling, and repair both sebaceous glands and epidermis in response to injury/loss of their resident progenitor cells. The Fuchs lab has shown that when introduced into the cytoplasm of unfertilized oocytes, mouse skin stem cells can become reprogrammed to generate all tissues of the animal. The team has also transcriptionally profiled these cells and identified a "molecular signature" of genes preferentially expressed in these stem cells. They've used these markers to trace the embryonic origins of the stem cell niche, and have used mouse genetics to uncover a transcriptional and epigenetic circuitry important for maintenance of the skin stem cells. By elucidating the mechanisms underlying how slow-cycling hair follicle stem cells become activated to regenerate a new hair with each cycle, the group has discovered that when uncontrolled, the very mechanisms underlying stem cell activation result in skin tumors, including pilomatricomas, trichofolliculomas and other cancers.
Nguyen H, Merrill BJ, Polak L, Nikolova M, Rendl M, Shaver TM, Pasolli HA, Fuchs E. Tcf3 and Tcf4 are essential for long-term homeostasis of skin epithelia. Nat Genet. 2009 Oct;41(10):1068-75.
Ezhkova E, Pasolli HA, Parker JS, Stokes N, Su IH, Hannon G, Tarakhovsky A, Fuchs E. Ezh2 orchestrates gene expression for the stepwise differentiation of tissue-specific stem cells. Cell. 2009 Mar 20;136(6):1122-35.
Greco V, Chen T, Rendl M, Schober M, Pasolli HA, Stokes N, Dela Cruz-Racelis J, Fuchs E. A two-step mechanism for stem cell activation during hair regeneration. Cell Stem Cell. 2009 Feb 6;4(2):155-69. Erratum in: Cell Stem Cell. 2009 May 8;4(5):464.
Nowak JA, Polak L, Pasolli HA, Fuchs E. Hair follicle stem cells are specified and function in early skin morphogenesis. Cell Stem Cell. 2008 Jul 3;3(1):33-43.
Yi R, Poy MN, Stoffel M, Fuchs E. A skin microRNA promotes differentiation by repressing 'stemness'. Nature. 2008 Mar 13;452(7184):225-9.
Horsley V, Aliprantis AO, Polak L, Glimcher LH, Fuchs E. NFATc1 balances quiescence and proliferation of skin stem cells. Cell. 2008 Jan 25;132(2):299-310.
Li J, Greco V, Guasch G, Fuchs E, Mombaerts P. Mice cloned from skin cells. Proc Natl Acad Sci U S A. 2007 Feb 20;104(8):2738-43.
Horsley V, O'Carroll D, Tooze R, Ohinata Y, Saitou M, Obukhanych T, Nussenzweig M, Tarakhovsky A, Fuchs E. Blimp1 defines a progenitor population that governs cellular input to the sebaceous gland. Cell. 2006 Aug 11;126(3):597-609.
Rhee H, Polak L, Fuchs E. Lhx2 maintains stem cell character in hair follicles. Science. 2006 Jun 30;312(5782):1946-9.
Lechler T, Fuchs E. Asymmetric cell divisions promote stratification and differentiation of mammalian skin. Nature. 2005 Sep 8;437(7056):275-80.
Blanpain C, Lowry WE, Geoghegan A, Polak L, Fuchs E. Self-renewal, multipotency, and the existence of two cell populations within an epithelial stem cell niche. Cell. 2004 Sep 3;118(5):635-48.
Tumbar T, Guasch G, Greco V, Blanpain C, Lowry WE, Rendl M, Fuchs E. Defining the epithelial stem cell niche in skin. Science. 2004 Jan 16;303(5656):359-63.