Skip to main content
eScholarship
Open Access Publications from the University of California

UC Santa Cruz

UC Santa Cruz Electronic Theses and Dissertations bannerUC Santa Cruz

Cellular and Molecular Mechanisms of Hematopoietic Stem Cell Regenerative Capacity Throughout Life

No data is associated with this publication.
Abstract

Hematopoiesis is the process by which all blood and immune cells are generated by hematopoietic stem cells (HSCs). As stem cells, HSCs can both self-renew and differentiate, and it is this regenerative capacity that is harnessed in the clinic to treat a multitude of hematologic malignancies. However, HSC reconstitution capacity is dynamic throughout life, specifically with regards to tissue-resident immune cells. Unlike circulating immune cells that are continuously generated from HSCs, many tissue-resident immune cells are of fetal origin and poorly generated from adult HSCs. Therefore, to improve the clinical utility of HSCs, it is essential to understand how tissue-resident immune cells are generated. Using lineage tracing, gene knock-out models and transplantation assays, we assessed the roles of Flk2 and IL7Rα in HSC tissue-resident immune cell reconstitution capacity. These studies uncovered an essential role of IL7Rα in tissue-resident lymphoid (TLC) development and generation and a more specific, temporal role in tissue-resident macrophage (TrMac) development. To further understand the epigenetic underpinnings of HSC regenerative capacity, we assessed chromatin accessibility in HSCs throughout life and discovered unique chromatin architecture that dictates age-specific functional differences. Together, this body of work identifies both cellular and molecular mechanisms of HSC reconstitution potential that may be targeted to ultimately improve HSC-based therapies.

Main Content

This item is under embargo until August 2, 2025.