# The regulation of melanocyte stem cells by Wnt signaling

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2024 · $464,042

## Abstract

Summary
Our long-term goal is to understand the precise location and molecular regulation of melanocyte stem cells
(McSCs), with a special emphasis on the role(s) of the Wnt pathway in regulating normal and abnormal McSCs.
Our previous studies reported that McSCs within the hair follicle (HF McSCs) can contribute to hair pigmentation
and possess the potential to produce epidermal melanocytes through activation of Wnt signaling. More recently,
we reported that oncogenic HF McSCs can transform into melanoma and demonstrated that Wnt signaling
crosstalks with mechanisms elicited by oncogenic mutations to drive melanomagenesis. Nonetheless, an
epidermal source of McSCs has been commonly proposed as the most likely contributor to skin MCs, skin
pigmentation and the majority of pigmentation disorders, including vitiligo, post-inflammatory hyperpigmentation,
and the deadly skin cancer melanoma, disorders that arise from interfollicular skin epidermis in humans. Thus,
during the last funding period, we asked a fundamental question “do McSCs also exist within the skin
epidermis?” Addressing this requires the examination of epidermal melanocytes for their self-sustainability and
regenerative capacities without contamination of HF McSCs, which possess the potential to give rise to MCs, at
least after skin wounding. The major challenge in the field has been the lack of a melanocyte-specific tool to
distinguish epidermal McSCs (epMcSCs) from HF McSCs in normal skin where numerous hair follicles are
present. Here, we have created a novel mouse model, OCA2-creERT, that solely targets pigmented epidermal
melanocytes without targeting HF McSCs. We have used this novel tool to demonstrate that OCA2+ epidermal
melanocytes are pigmented, yet self-sustaining, and possess the ability to regenerate during homeostasis and
proliferate and differentiate following physiological stimuli like UVB irradiation. These findings have led us to
hypothesize that Oca2+ MCs possess characteristics of stem cell/progenitor cells and perform
regenerative functions in the skin independent of HF McSCs. This new model provides us with the necessary
tools to address, in the next granting period, how Oca2+ MCs possess the lineage capacity to regenerate various
skin melanocytes while retaining a self-renewing capacity long-term (Aim1), how the Wnt signaling pathway
regulates their regenerative behavior in collaboration with other key signaling pathways (Aim2) and whether
OCA2+ epidermal melanocytes can be a cellular source for nevi with a potential for melanoma transformation
under the influence of Wnt signaling (Aim3).

## Key facts

- **NIH application ID:** 10889061
- **Project number:** 5R01AR059768-14
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Mayumi Ito
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $464,042
- **Award type:** 5
- **Project period:** 2011-08-05 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10889061

## Citation

> US National Institutes of Health, RePORTER application 10889061, The regulation of melanocyte stem cells by Wnt signaling (5R01AR059768-14). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10889061. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*