Valerie Horsley
Yale University, MCDB, Faculty Member
In recent years, several studies have shed light into the processes that regulate epidermal specification and homeostasis. We previously showed that a broad-spectrum γ-secretase inhibitor DAPT promoted early keratinocyte specification in... more
In recent years, several studies have shed light into the processes that regulate epidermal specification and homeostasis. We previously showed that a broad-spectrum γ-secretase inhibitor DAPT promoted early keratinocyte specification in human embryonic stem cells triggered to undergo ectoderm specification. Here, we show that DAPT accelerates human embryonic stem cell differentiation and induces expression of the ectoderm protein AP2. Furthermore, we utilize RNA sequencing to identify several candidate regulators of ectoderm specification including those involved in epithelial and epidermal development in human embryonic stem cells. Genes associated with transcriptional regulation and growth factor activity are significantly enriched upon DAPT treatment during specification of human embryonic stem cells to the ectoderm lineage. The human ectoderm cell signature identified in this study contains several genes expressed in ectodermal and epithelial tissues. Importantly, these genes a...
Research Interests:
Stratified squamous epithelial cells are found in a number of organs, including the skin epidermis and the thymus. The progenitor cells of the developing epidermis form a multi-layered epithelium and appendages, like the hair follicle, to... more
Stratified squamous epithelial cells are found in a number of organs, including the skin epidermis and the thymus. The progenitor cells of the developing epidermis form a multi-layered epithelium and appendages, like the hair follicle, to generate an essential barrier to protect against water loss and invasion of foreign pathogens. In contrast, the thymic epithelium forms a three-dimensional mesh of keratinocytes that are essential for positive and negative selection of self-restricted T cells. While these distinct stratified epithelial tissues derive from distinct embryonic germ layers, both tissues instruct immunity, and the epithelial differentiation programs and molecular mechanisms that control their development are remarkably similar. In this review, we aim to highlight some of the similarities between the thymus and the skin epidermis and its appendages during developmental specification.
Research Interests:
Understanding the epigenetic mechanisms that control the activation of adult stem cells holds the promise of tissue and organ regeneration. Hair follicle stem cells have emerged as a prime model to study stem cell activation.... more
Understanding the epigenetic mechanisms that control the activation of adult stem cells holds the promise of tissue and organ regeneration. Hair follicle stem cells have emerged as a prime model to study stem cell activation. Wnt/β-catenin signaling controls multiple aspects of skin epithelial regeneration, with its excessive activity promoting the hyperactivation of hair follicle stem/progenitor cells and tumorigenesis. The contribution of chromatin factors in regulating Wnt/β-catenin pathway function in these processes is unknown. Here, we show that chromatin effector Pygopus homolog 2 (Pygo2) produced by the epithelial cells facilitates depilation-induced hair regeneration, as well as β-catenin-induced activation of hair follicle stem/early progenitor cells and trichofolliculoma-like skin hyperplasia. Pygo2 maximizes the expression of Wnt/β-catenin targets, but is dispensable for β-catenin-mediated expansion of LIM/homeobox protein Lhx2(+) cells, in the stem/early progenitor cell...
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Extended abstract of a paper presented at Microscopy and Microanalysis 2008 in Albuquerque, New Mexico, USA, August 3 – August 7, 2008
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
The epidermis and its appendages, such as the hair follicle (HF), continually regenerate throughout postnatal mammalian life due to the activity of resident epithelial stem cells (SCs). The follicular SC niche, or the bulge, is composed... more
The epidermis and its appendages, such as the hair follicle (HF), continually regenerate throughout postnatal mammalian life due to the activity of resident epithelial stem cells (SCs). The follicular SC niche, or the bulge, is composed of a heterogeneous population of self-renewing multipotent cells. Multiple intrinsic molecular mechanisms promote the transition of follicular SCs from quiescence to activation. In addition, numerous extrinsic cell types influence the activity and characteristics of bulge cells. Ultimately, the balance between these intrinsic and extrinsic mechanisms influences the function of bulge cells during homeostasis and tissue regeneration and likely contributes to skin tumorigenesis. Here, we review both the intrinsic and extrinsic factors that contribute to the skin SC niche.
Research Interests:
Research Interests:
Research Interests:
Research Interests: Stem Cells, Immunohistochemistry, Stem Cell, Transcription Factors, Morphogenesis, and 14 moreGene expression, Biological Sciences, Mice, Animals, Cell, Skin, Cyclosporine, Cell nucleus, Biological markers, Cell Proliferation, Hair Follicle, Down-Regulation, Immunosuppressive Agents, and Medical and Health Sciences
Research Interests:
Research Interests:
We explore the mechanical properties of colonies of cohesive cells adherent on soft substrates. Specifically, we image the spatial distribution of traction stresses exerted by colonies of primary mouse keratinocytes on fibronectin-coated... more
We explore the mechanical properties of colonies of cohesive cells adherent on soft substrates. Specifically, we image the spatial distribution of traction stresses exerted by colonies of primary mouse keratinocytes on fibronectin-coated silicone gels. These cells ...