# Clonal dynamics and single cell transcriptomics of prostate luminal epithelial cells in homeostasis and aging

> **NIH NIH F99** · STATE UNIVERSITY NEW YORK STONY BROOK · 2021 · $32,532

## Abstract

PROJECT SUMMARY
 The most common prostate disorders, benign prostate enlargement and prostate cancer are associated with
aging and attributed to hormonal imbalances and loss of glandular homeostasis. Given the major impact prostate
pathologies have on men’s health and their significant burden on healthcare systems, it is important to further
elucidate the barriers posed by normal homeostasis to deregulated clonal growth. To date, most studies focused
on elucidating the identity of various stem cell prostate populations and on validating their stem cell potential in
culture assays. However, a precise understanding of the cellular and population dynamics at play in adult
prostate homeostasis, and how its fine balances change with aging and contribute to age-related cellular
hyperproliferations, has not emerged so far. Advances in this area would be extremely beneficial for identifying
deregulated prostate populations in aged tissues and for designing prophylactic therapies. In preliminary studies,
using in vivo lineage-tracing and single cell transcriptomics, I uncovered a “luminal intermediate” transcriptional
state (LumI) with unique Wnt/p63 signaling which constitutes a great portion of the cancer cell populations
expanding in early stages of tumorigenesis.
 In the F99 phase of the proposal, I will investigate the LumI cell state as the preferred cell of origin in cancer
models and the underlying growth program controlled by Wnt signaling and p63. Specifically, I will employ
functional organoid assays to investigate the role of Wnt signaling in promoting LumI cell growth in vitro and
delineate the effects of eliminating the Wnt/p63 signaling in vivo. In the K00 phase of the proposal, I will leverage
my methods and generate new mouse models to delineate the cellular level heterogeneity and growth patterns
in adult and aged prostate luminal layer and explore the underlying molecular regulatory mechanisms.
Specifically, I will utilize innovative mathematical modeling to integrate the clonal data obtained from genetic
lineage tracing to characterize the modes of adult and aging homeostatic growth adopted by prostate cells. I will
also generate a novel mouse model: Nkx3.1CreERT2/+-Confetti-CARLIN mouse for simultaneous in vivo lineage
tracing and barcoding which will provide increased lineage ancestry resolution. Single cell RNAseq and Single
cell ATACseq will be used to assess cellular states and uncover the dynamic molecular heterogeneity of prostate
luminal cells in the lineage tracing mouse model. The K00 Aim will provide a comprehensive functional map of
luminal prostate cells in adult and aging prostate and identify lineages and master regulator genes associated
with luminal clones.
 Taken together, my studies will provide a comprehensive understanding of population growth dynamics in
the luminal layer of prostate tissue and may lead to identification of novel therapeutic targets for age-related
prostate hyperproliferative disorders.

## Key facts

- **NIH application ID:** 10361741
- **Project number:** 1F99DK131481-01
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** Fu Luo
- **Activity code:** F99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $32,532
- **Award type:** 1
- **Project period:** 2021-09-15 → 2022-05-20

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10361741

## Citation

> US National Institutes of Health, RePORTER application 10361741, Clonal dynamics and single cell transcriptomics of prostate luminal epithelial cells in homeostasis and aging (1F99DK131481-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10361741. Licensed CC0.

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