# The regulation of melanocyte stem cells by Wnt signaling

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $372,900

## Abstract

SUMMARY
Abnormalities of skin melanocytes (Mcs) can cause a number of skin pigmentation diseases including
hyper/hypo skin pigmentation, as well as the most aggressive form of skin cancer, melanoma, that still lacks a
cure. One of the major obstacles in developing effective treatments for melanoma as well as many other
pigmentary disorders is our poor understanding of the organization and regulation of Mc stem cells (McSCs).
Thus far, McSCs have been only identified in the hair follicle, and it is not known whether McSCs are present in
the skin epidermis. Moreover, little is known about how McSCs are molecularly regulated. This is in stark
contrast to epithelial stem cells whose identity and characterization have been key to interrogating this
population and determining how epithelial stem cells are regulated during tissue regeneration as well as during
carcinogenesis. During the last granting period, we made two important discoveries: First, we found that Wnt
signaling regulates the self-renewal and differentiation of McSCs as well as their melanoma-transformation in
an established melanoma mouse model. Second, we found that a subpopulation of Mcs in the epidermis also
displays active Wnt signaling, and these epidermal Mcs persist for long-term within the epidermis. We
hypothesize that Wnt-active epidermal Mcs represent a McSC population that maintains and
regenerates Mcs in the skin epidermis and can transform into melanoma cells. We will test this hypothesis
in three Specific Aims. Under Aim1, we will perform in vivo genetic lineage analysis under normal homeostasis
and during Mc proliferation following UV exposure in parallel with ex vivo skin/hair reconstitution assays to
determine whether Wnt-active epidermal Mcs self-renew and differentiate to durably maintain epidermal or hair
Mcs. Under Aim 2, we will examine how Wnt signaling regulates the behavior of epidermal Mcs under normal
homeostasis and following UV exposure. For this, we will perform Wnt loss- and gain-of-function experiments in
Mcs employing established genetic mouse models. Under Aim3, we will test the ability of epidermal Mcs to
form melanoma upon expression of melanoma-inducing mutations in a transplantation model. In summary, this
study will be the first to definitively address the presence of McSCs within the skin epidermis and to begin to
define how epidermal McSCs are regulated. Our findings will have a major impact in the field of Mc and
melanoma biology. Newly identified McSCs within the skin epidermis and the Wnt pathway that regulates their
behavior will provide novel targets for the prevention and treatment of melanoma as well as various
pigmentation diseases.

## Key facts

- **NIH application ID:** 9975710
- **Project number:** 5R01AR059768-10
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Mayumi Ito
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $372,900
- **Award type:** 5
- **Project period:** 2011-08-05 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9975710

## Citation

> US National Institutes of Health, RePORTER application 9975710, The regulation of melanocyte stem cells by Wnt signaling (5R01AR059768-10). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9975710. Licensed CC0.

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