Dermatology; Epithelial Cells; Molecular Biology; Regeneration; Skin Diseases; Stem Cells; Tissue Survival
Obesity Research Working Group
Postnatal Development & Regeneration
Stem Cell Center, Yale: Stem Cell Niche and Homing | Tissue Specific Stem Cells
Our laboratory studies the cellular and molecular mechanisms that control stem cell activity and function within epithelia, the tissues that line our internal organs and outer surfaces. We use the mouse as a genetic model system to study how adult stem cells within epithelial tissues maintain tissue homeostasis, wound healing and can contribute to cancer formation. The primary epithelial tissue we use is the mammalian skin, which contains multiple stem cell populations and forms a complex tissue that protects our bodies from external pathogens and loss of internal bodily fluids. Mammalian skin is an excellent model to study developmental and stem cell biology because the epidermis and its appendages are in a constant state of regeneration, which is actively sustained by tissue stem cells.
Our vision is to understand the cellular and molecular regulation of epithelial tissue development and regeneration. We focus on both the intrinsic transcriptional as well as the extrinsic signaling mechanisms that control these processes.
NFATc1 balances quiescence and proliferation of skin stem cells.
V. Horsley, A. O. Aliprantis, L. Polak, L.H.Glimcher and E. Fuchs. (2008). NFATc1 balances quiescence and proliferation of skin stem cells. Cell. 132(2):299-310.
Blimp1 defines a novel progenitor population that governs cellular input to the sebaceous gland.
V. Horsley, D. O’Carroll, R. Tooze, Y. Ohinata, M.Saitou, T. Obukhanych, M. Nussenzweig, A. Tarakhovsky and E. Fuchs. (2006). Blimp1 defines a novel progenitor population that governs cellular input to the sebaceous gland. Cell. 126(3):597-609.
Adipocyte precursor cells contribute to the skin stem cell niche.
E. Festa, J. Fretz, R. Berry, B. Schmidt, M. Rodeheffer, M. Horowitz and V. Horsley. (2011) Adipocyte precursor cells contribute to the skin stem cell niche. Cell. 146(5): 761-771.
Intradermal adipocytes regulate fibroblast function during skin wound healing.
B. Schmidt and V. Horsley. (2013) Intradermal adipocytes regulate fibroblast function during skin wound healing. Development. 140(7): 1517-27.
Intercellular adhesions organize epithelial cell-matrix mechanics.
A. F. Mertz, Y. Che, S. Banerjee, J. Goldstein, S. Revilla, C. Niessen, M. C. Marchetti, E. R. Dufresne and V. Horsley (2013). Intercellular adhesions organize epithelial cell-matrix mechanics. PNAS. 110(3):842-7.
Transcriptional profiling of keratinocyte specification in human embryonic stem cells.
A. Tadeu, S. Lin, L. Hou, L. Chung, M. Zhong, H. Zhoa and V. Horsley. (2015) Transcriptional profiling of keratinocyte specification in human embryonic stem cells. Plos One. 10: e0122493.
Edges of human embryonic stem cell colonies display distinct mechanical properties and differentiation potential.
K. Rosowski, A. Mertz, S. Norcross, E. Dufresne, and V. Horsley. (2015) Edges of human embryonic stem cell colonies display distinct mechanical properties and differentiation potential. Sci. Rep. 5: 14218.
Nuclear-cytoskeletal linkages facilitate cross talk between the nucleus and intercellular adhesions.
R. Stewart, A. Zubek, K. Rosowski, S. Schreiner, V. Horsley*, and M. King* (*co-corresponding author). (2015) LINC complexes support hair follicle integrity and intercellular adhesion. J. Cell Biol. 209: 403-18.
Loss of endogenous Nfatc1 reduces the rate of DMBA/TPA-induced skin tumorigenesis.
J. Goldstein, E. Roth, N. Roberts, R. Zwick, S. Lin, S. Fletcher, A. Tadeu, C. Wu, A. Beck, C. Zeiss, M. Suarez-Farinas and V. Horsley. (2015) Loss of endogenous Nfatc1 reduces the rate of DMBA/TPA-induced skin tumorigenesis. Mol. Biol. Cell. pii: mbc.E15-05-0282.
Skin Adipocyte Stem Cell Self-Renewal Is Regulated by a PDGFA/AKT-Signaling Axis
G. C. Rivera-Gonzalez, B.A. Shook, B. Holtrup, K. Bollag, M. S. Rodeheffer and V. Horsley. (2016) Adipocyte stem cell self-renewal is regulated by a Pdgfa/Akt signalling axis in the skin. Cell Stem Cell. 2016 Oct 1. pii: S1934-5909(16)30296-X. In Press.
Full List of PubMed Publications
- Rübsam M, Mertz AF, Kubo A, Marg S, Jüngst C, Goranci-Buzhala G, Schauss AC, Horsley V, Dufresne ER, Moser M, Ziegler W, Amagai M, Wickström SA, Niessen CM: E-cadherin integrates mechanotransduction and EGFR signaling to control junctional tissue polarization and tight junction positioning. Nat Commun. 2017 Nov 1; 2017 Nov 1. PMID: 29093447
- Rivera-Gonzalez GC, Shook BA, Horsley V: PDGFA regulation of dermal adipocyte stem cells. Stem Cell Investig. 2017; 2017 Sep 7. PMID: 29057244
- Roberts NA, Adams BD, McCarthy NI, Tooze RM, Parnell SM, Anderson G, Kaech SM, Horsley V: Prdm1 Regulates Thymic Epithelial Function To Prevent Autoimmunity. J Immunol. 2017 Aug 15; 2017 Jul 12. PMID: 28701508
- Horsley V, Naik S: Tregs Expand the Skin Stem Cell Niche. Dev Cell. 2017 Jun 5. PMID: 28586641
- Horsley V, Watt F: Repeal and Replace: Adipocyte Regeneration in Wound Repair. Cell Stem Cell. 2017 Apr 6. PMID: 28388424
- Rivera-Gonzalez GC, Shook BA, Andrae J, Holtrup B, Bollag K, Betsholtz C, Rodeheffer MS, Horsley V: Skin Adipocyte Stem Cell Self-Renewal Is Regulated by a PDGFA/AKT-Signaling Axis. Cell Stem Cell. 2016 Dec 1; 2016 Oct 13. PMID: 27746098
- Shook B, Rivera Gonzalez G, Ebmeier S, Grisotti G, Zwick R, Horsley V: The Role of Adipocytes in Tissue Regeneration and Stem Cell Niches. Annu Rev Cell Dev Biol. 2016 Oct 6; 2016 May 4. PMID: 27146311
- Shook B, Xiao E, Kumamoto Y, Iwasaki A, Horsley V: CD301b+ Macrophages Are Essential for Effective Skin Wound Healing. J Invest Dermatol. 2016 Sep; 2016 Jun 7. PMID: 27287183
- Belinsky GS, Sreekumar B, Andrejecsk JW, Saltzman WM, Gong J, Herzog RI, Lin S, Horsley V, Carpenter TO, Chung C: Pigment epithelium-derived factor restoration increases bone mass and improves bone plasticity in a model of osteogenesis imperfecta type VI via Wnt3a blockade. FASEB J. 2016 Aug; 2016 Apr 28. PMID: 27127101
- Horsley V, Kulesz-Martin M, Wang XJ: Montagna Symposium 2015: Harnessing Stem Cells to Reveal Novel Skin Biology and Disease Treatments. J Invest Dermatol. 2016 May. PMID: 27107373
- Ebmeier S, Horsley V: Origin of fibrosing cells in systemic sclerosis. Curr Opin Rheumatol. 2015 Nov. PMID: 26352735
- Alexander CM, Kasza I, Yen CL, Reeder SB, Hernando D, Gallo RL, Jahoda CA, Horsley V, MacDougald OA: Dermal white adipose tissue: a new component of the thermogenic response. J Lipid Res. 2015 Nov; 2015 Sep 24. PMID: 26405076
- Goldstein J, Roth E, Roberts N, Zwick R, Lin S, Fletcher S, Tadeu A, Wu C, Beck A, Zeiss C, Suárez-Fariñas M, Horsley V: Loss of endogenous Nfatc1 reduces the rate of DMBA/TPA-induced skin tumorigenesis. Mol Biol Cell. 2015 Oct 15; 2015 Aug 26. PMID: 26310443
- Rosowski KA, Mertz AF, Norcross S, Dufresne ER, Horsley V: Edges of human embryonic stem cell colonies display distinct mechanical properties and differentiation potential. Sci Rep. 2015 Sep 22; 2015 Sep 22. PMID: 26391588
- Stewart RM, Zubek AE, Rosowski KA, Schreiner SM, Horsley V, King MC: Nuclear-cytoskeletal linkages facilitate cross talk between the nucleus and intercellular adhesions. J Cell Biol. 2015 May 11. PMID: 25963820
- Tadeu AM, Lin S, Hou L, Chung L, Zhong M, Zhao H, Horsley V: Transcriptional profiling of ectoderm specification to keratinocyte fate in human embryonic stem cells. PLoS One. 2015; 2015 Apr 7. PMID: 25849374
- Roberts N, Horsley V: Developing stratified epithelia: lessons from the epidermis and thymus. Wiley Interdiscip Rev Dev Biol. 2014 Nov-Dec; 2014 Aug 29. PMID: 25176390
- Sun P, Watanabe K, Fallahi M, Lee B, Afetian ME, Rheaume C, Wu D, Horsley V, Dai X: Pygo2 regulates β-catenin-induced activation of hair follicle stem/progenitor cells and skin hyperplasia. Proc Natl Acad Sci U S A. 2014 Jul 15; 2014 Jun 30. PMID: 24982158
- Jeffery E, Berry R, Church CD, Yu S, Shook BA, Horsley V, Rosen ED, Rodeheffer MS: Characterization of Cre recombinase models for the study of adipose tissue. Adipocyte. 2014 Jul 1; 2014 Jun 27. PMID: 25068087
- Goldstein J, Fletcher S, Roth E, Wu C, Chun A, Horsley V: Calcineurin/Nfatc1 signaling links skin stem cell quiescence to hormonal signaling during pregnancy and lactation. Genes Dev. 2014 May 1; 2014 Apr 14. PMID: 24732379
- Rivera-Gonzalez G, Shook B, Horsley V: Adipocytes in skin health and disease. Cold Spring Harb Perspect Med. 2014 Mar 1; 2014 Mar 1. PMID: 24591537
- Tadeu AM, Horsley V: Epithelial stem cells in adult skin. Curr Top Dev Biol. 2014. PMID: 24439804
- Tadeu AM, Horsley V: Notch signaling represses p63 expression in the developing surface ectoderm. Development. 2013 Sep; 2013 Aug 7. PMID: 23924630
- McGee HM, Schmidt BA, Booth CJ, Yancopoulos GD, Valenzuela DM, Murphy AJ, Stevens S, Flavell RA, Horsley V: IL-22 promotes fibroblast-mediated wound repair in the skin. J Invest Dermatol. 2013 May; 2012 Dec 6. PMID: 23223145
- Schmidt BA, Horsley V: Intradermal adipocytes mediate fibroblast recruitment during skin wound healing. Development. 2013 Apr. PMID: 23482487
- Mertz AF, Che Y, Banerjee S, Goldstein JM, Rosowski KA, Revilla SF, Niessen CM, Marchetti MC, Dufresne ER, Horsley V: Cadherin-based intercellular adhesions organize epithelial cell-matrix traction forces. Proc Natl Acad Sci U S A. 2013 Jan 15; 2012 Dec 31. PMID: 23277553
- Schmidt B, Horsley V: Unravelling hair follicle-adipocyte communication. Exp Dermatol. 2012 Nov. PMID: 23163647
- Horsley V: Split decisions: oesophageal progenitor cell behaviour. EMBO J. 2012 Sep 12; 2012 Aug 10. PMID: 22885597
- Goldstein J, Horsley V: Home sweet home: skin stem cell niches. Cell Mol Life Sci. 2012 Aug; 2012 Mar 13. PMID: 22410738
- Mertz AF, Banerjee S, Che Y, German GK, Xu Y, Hyland C, Marchetti MC, Horsley V, Dufresne ER: Scaling of traction forces with the size of cohesive cell colonies. Phys Rev Lett. 2012 May 11; 2012 May 8. PMID: 23003091
- Festa E, Fretz J, Berry R, Schmidt B, Rodeheffer M, Horowitz M, Horsley V: Adipocyte lineage cells contribute to the skin stem cell niche to drive hair cycling. Cell. 2011 Sep 2. PMID: 21884937
- Horsley V: Upward bound: follicular stem cell fate decisions. EMBO J. 2011 Aug 3; 2011 Aug 3. PMID: 21811300
- Horsley V: Epigenetics, Wnt signaling, and stem cells: the Pygo2 connection. J Cell Biol. 2009 Jun 1. PMID: 19487452