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

> **NIH NIH R01** · CORNELL UNIVERSITY · 2021 · $339,563

## Abstract

Abstract
Despite the crucial importance of the inter-follicular epidermis (IFE) for the essential body barrier function,
molecular characterization of the stem cells (SCs) within the basal layer has not been achieved. This impairs
our ability to study the mechanisms that specifically control IFE SCs for proper homeostasis and wound
healing and to understand how these mechanisms may be affected in skin disease and aging. The IFE SCs
have been traditionally identified in vivo as DNA label retaining cells (LRCs) while transit amplifying (TA) or
progenitor cells were considered non-LRCs. However, LRC and non-LRC markers to unambiguously test this
model in vivo had been lacking. Using our H2B-GFP pulse-chase transgenic mouse system, we label IFE
LRCs and non-LRCs, define mRNA expression profiles, and find that these cells are molecularly distinct. In our
first set of preliminary data, we demonstrate that, contrary to the expectation that SC are frequently dividing
cells, both of our IFE cellular subsets of LRCs (marked by Dlx1CreER) and of non-LRCs (marked by Slc1a3CreER)
act as two independent SCs in long-term lineage tracing. Collectively, our data support a model in which the
IFE is a heterogeneous tissue, being composed of molecularly distinct domains or territories, which are
spatially patterned relative to each other and to skin landmarks. These territories are enriched in LRCs and
non-LRCs, regenerate at different rates, and contain distinct SCs and differentiated cells that can be defined as
molecularly discrete IFE cellular subsets. We provide LRC and non-LRC-enriched markers and genetic
labeling tools that define novel IFE cellular subsets, which will enable us to rigorously examine the newly
uncovered IFE heterogeneity. The specific objectives are to: (i) examine the organization of IFE territories
throughout life, and determine relative SC potential of newly uncovered IFE cellular subsets; (ii) validate and
refine markers of IFE heterogeneity from our newly uncovered undifferentiated and differentiated IFE cellular
subsets; and (iii) unravel mechanism of IFE heterogeneity by focusing on two transcription factors we identified
in our LRC versus non-LRC IFE subsets. Collectively, our data will constitute a key for understanding
previously un-recognized cellular and molecular heterogeneity within the IFE and provide a new entry point into
SC regulation in this essential, yet poorly understood skin compartment.

## Key facts

- **NIH application ID:** 10132185
- **Project number:** 5R01AR070157-05
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Tudorita Tumbar
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $339,563
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10132185

## Citation

> US National Institutes of Health, RePORTER application 10132185, Defining the heterogeneity of cell lineages in the inter-follicular epidermis (5R01AR070157-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10132185. Licensed CC0.

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