# Posttranscriptional control of epidermal progenitors senescence

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $364,625

## Abstract

Summary/Abstract
Adult organs are maintained through a tightly regulated balance of proliferation, differentiation,
and self-renewal of stem cells, during normal tissue homeostasis or tissue repair. In recent
years stratified squamous epithelia such as the epidermis with its high degree of turnover and
ability to withstand perhaps the highest number of injuries have become the “gold standard” for
models of progenitor cell homeostasis. The basal layer of the interfollicular epidermis consists of
rare quiescent and more prevalent actively cycling stem and progenitor cells. The proliferating
basal keratinocytes are responsible for constant tissue regeneration and are characterized by
increased metabolism coupled with prevention of commitment to differentiation. At the same
time, the actively cycling stem and progenitor cells need to be protected from the risk of
undergoing senescence associated with their intense proliferative state. Therefore, the main
focus of this application is to elucidate the molecular pathways preventing senescence
phenotypes in proliferating epidermal progenitor cells during steady state homeostasis and
damage-driven tissue regeneration. In our recently published work and preliminary studies we
applied an unbiased, systematic approach to capture the mRNA binding proteins of epidermal
progenitors and identified YBX1 (Y-box binding protein-1) as a critical effector of progenitor
function. YBX1 expression is restricted to the cycling epidermal progenitors and its genetic
ablation leads to defects in in the architecture of the epidermis. We uncovered that YBX1
negatively controls epidermal progenitor senescence by regulating the translation of a
senescence-associated subset of cytokine mRNAs via their 3’ untranslated regions (UTRs). We
are now proposing to investigate the molecular mechanisms of the YBX1 driven epidermal
deficiencies and also to test the hypothesis that dysregulation of YBX1 in the epidermis
promotes altered homeostatic and injury-induced regeneration. We will define the biochemical
machinery underlying YBX1 driven regulation of senescence-associated cytokines, its biological
significance for keratinocyte progenitor function and ability to execute cell fate decisions.
Together, these studies are positioned to identify a novel level of translation-associated control
of senescence and cytokine production in the epidermis in vitro and in vivo.

## Key facts

- **NIH application ID:** 9880397
- **Project number:** 5R01AR075421-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Ya-Chieh Hsu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $364,625
- **Award type:** 5
- **Project period:** 2019-03-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9880397

## Citation

> US National Institutes of Health, RePORTER application 9880397, Posttranscriptional control of epidermal progenitors senescence (5R01AR075421-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9880397. Licensed CC0.

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