Hsu Lab | HSCRB

Hsu Lab Research

Beauty is skin deep

We use a multi-disciplinary approach including high-resolution imaging, lineage-tracing, mouse genetics, in utero surgery, flow cytometry, viral mediated rapid in vivo gene-editing, and single-cell genomics, to explore diverse cell-cell interactions in the skin during development, regeneration, and injury repair.

Areas of Investigation

The Cellular and Molecular Identity of the Stem Cell Niche

Stem cell behaviors are heavily influenced by the niche microenvironment, where stem cells reside. However, the identity of niche factors and niche cell types remains elusive for many mammalian stem cells. We have established tools and strategies to manipulate gene expression in numerous skin cell types and are using them to investigate reciprocal interactions between stem cells and niches. This research will define mechanisms that could be targeted to promote tissue regeneration or wound healing.

More about this work

Our current research focus in this area includes:

Feedback regulation by stem cell progeny

We have pioneered studies to identify stem cell progeny as important regulators of activity of parental stem cells (Hsu et al., Cell 2011, Hsu et al., Cell 2014). Currently, we are identifying specific signaling factors that govern this feedback regulation.

Identification of novel niche cell types and signals

With new tools that we established, we are systematically identifying novel cell types and secreted factors that govern stem cell quiescence, promote stem cell self-renewal, and instruct stem cell fate decisions. We are broadly interested in a wide variety of cell types. Current interests include the interactions between stem cells and nerves, immune cells, adipocytes, and fibroblasts.

Modification of stem cell behavior to enhance wound repair

More than 100 million people develop scars each year as a result of trauma, surgery, or burns. At least 6 million people suffer from chronic non-healing wounds (including diabetic foot ulcers and bedsores). We are applying what we have learned about how the niche regulates skin stem cells to develop novel wound healing strategies.

Scientific image: rows of cells, stained green, red, yellow

Function and Biology of Transit-Amplifying Cells

Somatic stem cells are often quiescent but occasionally divide to generate “transit-amplifying cells” (TACs). TACs then undergo rapid division and expansion to produce a large quantity of differentiated cells downstream. Since TACs are the workforce of tissue production while stem cells are mostly dormant, TACs are located at an ideal juncture to orchestrate production of their own downstream progeny with critical changes in surrounding niche cell types that accommodate and support a regenerating tissue (see our review comparing TACs in the blood and the skin (Zhang and Hsu WIREs Developmental Biology).

More about this work

Current projects relevant to TAC biology include:

TACs of one tissue control changes in many neighboring tissues

How tissues of different lineage grow together in an organ is a fundamental question in developmental biology. We discovered that hair follicle TACs control growth of the hair follicle itself and production of neighboring dermal adipocytes, coupling activity of two lineages (Zhang et al, G&D 2016). Currently, we are defining TAC function in regulating other tissues in the skin.

TACs and chemotherapy-related side effects

The highly proliferative nature of TACs is what makes them, not slow-cycling stem cells, a primary target of cytotoxic chemotherapies. Thus, understanding TAC function may inform strategies to prevent chemotherapy-related damage to tissues and organs. By studying the biology of TACs, we have discovered the root causes for several chemotherapy-related side effects, including hair loss, delayed wound healing, and susceptibility to infections. We are working on the cellular and molecular mechanisms leading to these phenotypes.

How Systemic Changes Regulate Stem Cell Behavior

Stem cells must respond not just to the niche but to systemic signals in response to stress, pregnancy, or aging. We have established approaches to determine if and how changes in systemic factors influence cell-cell interactions, stem cell behavior, and repair of injury in the skin. We have defined several circulating factors crucial for skin stem cell function and are determining whether these factors act directly or through the niche to regulate stem cell activity and tissue regeneration.