# Defining the heterogeneity of cell lineages in the inter-follicular epidermis

> **NIH NIH R01** · CORNELL UNIVERSITY · 2024 · $533,234

## Abstract

Abstract
Adult skin interfollicular epidermis (IFE) renewal is currently described by simple models of
relatively homogenous basal stem/progenitor cells. However, long-term IFE renewal is likely
orchestrated by the physiological demands of a complex tissue architecture comprising multiple
levels of heterogeneity. We began to elucidate the cellular and molecular organization of two
spatially distinct IFE domains, their physiological relevance, and the relationship between mouse
and human skin. We demonstrate that molecular and cellular states of mouse tail basal
microdomains (scales and inter-scales) recapitulate human skin IFE spatial organization in rete
ridges and inter-ridges. We begin to uncover a physiological relevance for the skin spatial
domains: adaptation to differential UV exposure. We identify multiple IFE populations with distinct
behavior in clonal analysis and describe the first in vivo epidermal transit-amplifying (TA) cell. The
later uniquely displays a maturation-dependent behavior with a timed-transition from an
amplification phase to an extinction phase. This opens-up a new road for investigating molecular
mechanisms of timed transitions from a ‘young’ to a ‘mature’ cell state. Using mouse genetics, we
develop new tools to label and characterize IFE domains that are most UV exposed and examine
in depth: (1) IFE spatial heterogeneity and domain organization in skin and its physiological
significance; and (2) the heterogeneity of IFE stem/TA population behavior in skin, how this
relates to regeneration capacity of spatial domains, and what are the mechanisms of cell fate
transition from a young to a mature TA cell state, and from a stem to a TA cell. We propose that
the extraordinary IFE complexity of basal cell states, multiple stem/TA cell populations, and spatial
organization may explain the unusual robustness of skin homeostasis in response to
constant environmental challenges.

## Key facts

- **NIH application ID:** 10827941
- **Project number:** 5R01AR070157-07
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Tudorita Tumbar
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $533,234
- **Award type:** 5
- **Project period:** 2023-04-12 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10827941

## Citation

> US National Institutes of Health, RePORTER application 10827941, Defining the heterogeneity of cell lineages in the inter-follicular epidermis (5R01AR070157-07). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10827941. Licensed CC0.

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