# Resolving the Hierarchy and Regulation of Sebaceous Gland Stem Cells

> **NIH NIH F31** · UNIVERSITY OF PENNSYLVANIA · 2021 · $46,036

## Abstract

PROJECT SUMMARY
Sebaceous glands (SGs) are appendages of mammalian skin that produce and secrete a mixture of lipids, known
as sebum. Sebum production is crucial for skin maintenance and deviations in normal sebaceous lipid production
are implicated in several skin pathologies including acne vulgaris and alopecia. Sebum production is carried out
by sebocytes, the constituent cell population of SGs. Sebocytes undergo a unique maturation process which
culminates with the rupture of the cell membrane. This process, termed holocrine secretion, facilitates the
secretion of sebum from SGs, but consequently results in sebocyte death. As lipid turnover is a function of
sebocyte turnover, sebocyte replenishment is critical to the functional maintenance of SGs. The lifelong turnover
of sebocytes requires a continuous supply of cells to replenish and maintain the gland, which suggests the
involvement of stem cells in the maintenance of SG tissues. However, the intrinsic and extrinsic mechanisms
that regulate activity of the presumptive SG stem cells are not well defined. This is in part due to the limitations
of static histological analyses. Such experimental approaches can only capture single snapshots in time, which
are insufficient for delineating a hierarchical organization in a tissue with a rapid turnover rate. Furthermore, the
overlapping expression of stem cell-associated genes, like Sox9, between the hair follicle and SGs has limited
our ability to interpret the functional role of these markers in SG physiology uncoupled from the hair. To overcome
these limitations, I have combined genetic lineage-tracing tools with live imaging approaches based on two-
photon microscopy. The overall goal of this study is to implement an integrative approach by combining a live
imaging system with state-of-the-art genomics tools to 1) characterize stem cell dynamics in SG homeostasis
and regeneration by live imaging, and 2) analyze how sebocyte fate is influenced by the key molecular signal,
Sox9. In my preliminary experiments, I found that cells from the hair follicle isthmus, an adjacent compartment,
made cell contributions to SGs, and that skin-specific knockouts of Sox9 resulted in SG atrophy. I hypothesize
that sebocytes are replenished by a heterogeneous stem cell population from the isthmus and that SOX9 is
required for their regulation and SG physiology. Aim 1 of this proposal is designed to resolve the sebocyte
lineage hierarchy and test the necessity of the isthmus in SG regeneration. Aim 2 of this proposal will address
the functional role of SOX9 in regulating sebocyte fate. This research offers an innovative approach to study SG
stem cells within the natural tissue environment by combining cutting-edge imaging technologies and genetic
tools. The goal of this proposal is to uncover the fundamental mechanisms of SG maintenance by resolving the
sebocyte lineage and molecular pathways that regulate SG stem cell activity in the skin.

## Key facts

- **NIH application ID:** 10313387
- **Project number:** 1F31AR079899-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Gabriella Rice
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $46,036
- **Award type:** 1
- **Project period:** 2021-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10313387

## Citation

> US National Institutes of Health, RePORTER application 10313387, Resolving the Hierarchy and Regulation of Sebaceous Gland Stem Cells (1F31AR079899-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10313387. Licensed CC0.

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