Transcriptomic and Proteomic Studies of Intercellular Communication Between Melanocytes and Keratinocytes in Human Skin

Author

Gabriella Stephanne Spitz-Becker

Date of Award

2022

Document Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

RU Laboratory

Simon Laboratory

Abstract

The epidermis is a stratified epithelium composed of multiple cell types. Keratinocytes are the most prevalent cells in the epidermis and provide the barrier function of the skin. Interspersed amongst the keratinocytes in the basal layer of the epidermis are melanocytes, the pigment producing cells of the epidermis. Melanocytes produce melanin pigment which resides in melanosomes, organelles that are transferred to keratinocytes. In my thesis work, I focused on identifying downstream results of intercellular communication between melanocytes and keratinocytes for each of these cell types. I characterized the transcriptomes of human melanocytes and keratinocytes that were freshly derived from human tissue in Chapter 2. These data served as a reference for comparison and validation for the work that followed. In Chapter 3, I studied the effect of the presence of melanocytes on keratinocyte gene expression. I identified Neuronal Cell Adhesion Molecule (NRCAM) as being upregulated in keratinocytes in the presence of melanocytes, which is the first suggestion of a role for NRCAM in melanocyte-keratinocyte interactions. In Chapter 4, I studied the effects of endothelin-1 (ET-1), a signaling molecule produced by keratinocytes, on melanocyte gene expression. I found that genes involved in cell morphology, neurite growth, and cytoskeletal organization were upregulated in melanocytes in response to ET-1. I specifically identified microtubule associated protein 2 (MAP2) as being upregulated in response to ET-1, which suggests a mechanism for how ET-1 induces changes in melanocyte morphology. I also found that the nerve growth factor receptor (NGFR) is upregulated in melanocytes in response to ET-1. This reveals a new locus of interaction between two cell-cell signaling pathways in melanocytes and keratinocytes. In Chapter 5, I used a proteomic approach to study keratinocyte phagosomes. This is the first such proteomic characterization of phagosomes from an epithelial cell. In the final chapter of my thesis, I outlined the immediate future directions of this work, and discussed how these basic biological findings may be applied to our understanding of disease states.

Comments

A Thesis Presented to the Faculty of The Rockefeller University in Partial Fulfillment of the Requirements for the degree of Doctor of Philosophy

Recommended Citation

Spitz-Becker, Gabriella Stephanne, "Transcriptomic and Proteomic Studies of Intercellular Communication Between Melanocytes and Keratinocytes in Human Skin" (2022). Student Theses and Dissertations. 663.
https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/663