# Intrinsic and extrinsic control of epithelial tissue stem cell activity

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA-IRVINE · 2022 · $448,029

## Abstract

PROJECT SUMMARY
 Tissue stem cells are rare, undifferentiated cells that are capable of self-renewal and are essential for
fueling the homeostasis and regeneration of the tissue in which they reside. They are often quiescent, and
when activated, they proliferate and differentiate to produce mature cell types with specialized functions. Stem
cell activities are jointly controlled by the intrinsic gene expression program and the signals from the
surrounding tissue microenvironment. Dissecting the intrinsic and extrinsic mechanisms that govern stem cell
quiescence and activation is important not only for gaining fundamental knowledge of tissue and stem cell
biology, but also for understanding how to manipulate cell fates in tissue engineering and regenerative
medicine. Myriad regenerative epithelial tissues, such as mammary gland, skin, and prostate, house stem cells
in their basal cell compartment. We use two mammalian tissues, mammary gland and skin, each with its
unique advantages and clinical relevance, as complimentary model systems to study both general and tissue-
specific mechanisms underlying the regulation of basal cell fate and stem cell activities. Our research has
elucidated the function of key transcription and chromatin factors in mammary and skin basal/stem cell gene
regulation, and how these factors interface with major signaling pathways to control the activation, proliferation,
differentiation, and epithelial-mesenchymal plasticity of basal stem cells. The recent advent of single-cell
sequencing technology has enabled us to systematically probe the cellular and molecular heterogeneities of
mammary and skin basal cells, allowing a deeper and more comprehensive understanding of their
compositions and characteristics as well as providing novel insights into the sequence of events in stem cell
activation and differentiation. In the next five years, we will continue to employ a multi-disciplinary approach
combining single-cell genomics and spatial gene expression mapping with tissue-specific gene knockout and
lineage tracing, in vivo and ex vivo stem cell assays, as well as molecular studies to address two major
knowledge gaps regarding mammary basal stem cells: how their quiescence is maintained and active
expansion is achieved. Specifically, we will test the innovative hypothesis that a low level of Wnt/b-catenin
signaling and molecular cross-talks between basal cells and specific macrophage subsets are critical for
maintaining basal stem cell quiescence. We will also characterize the novel function and regulation of a newly
discovered subset of basal cells as transit amplifying progenitor cells that serve as workhorses to drive basal
cell expansion during mammary epithelial morphogenesis, homeostasis, and regeneration. When and where
applicable, we will perform parallel analysis on skin in order to identify potentially general principles and
strategies underlying basal cell-macrophage cross-talks. Our findings will expose novel intr...

## Key facts

- **NIH application ID:** 10406792
- **Project number:** 1R35GM145307-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Xing Dai
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $448,029
- **Award type:** 1
- **Project period:** 2022-06-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10406792

## Citation

> US National Institutes of Health, RePORTER application 10406792, Intrinsic and extrinsic control of epithelial tissue stem cell activity (1R35GM145307-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10406792. Licensed CC0.

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