Understanding the Organization and Function of Diverse Stem Cell Niche Architectures
Date of Award
Spring 2023
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Genetics
First Advisor
Greco, Valentina
Abstract
Stem cells’ ability to build and replenish tissues depends on support from their niche. While niche architecture varies across different organs, the functional importance of niche architecture is unclear. During hair follicle growth, multipotent epithelial progenitors build hair via crosstalk with their remodeling fibroblast niche, the dermal papilla, providing a powerful model to functionally interrogate different niche architectures. Through intravital imaging, we show that dermal papilla fibroblasts remodel both individually and collectively to form a polarized, structurally robust niche. Polarized TGFβ signaling precedes structural niche polarity, and loss of TGFβ signaling in dermal papilla fibroblasts leads them to progressively lose their stereotypic architecture and instead surround the epithelium. The reorganized niche relocates multipotent progenitors, but nevertheless supports their proliferation and differentiation. However, progenitor differentiation is completed prematurely, resulting in compromised shorter hair production. Overall, my thesis work reveals that niche architecture optimizes organ efficiency, but is not absolutely essential for organ function.
Recommended Citation
Wei, Haoyang, "Understanding the Organization and Function of Diverse Stem Cell Niche Architectures" (2023). Yale Graduate School of Arts and Sciences Dissertations. 979.
https://elischolar.library.yale.edu/gsas_dissertations/979
