Transcriptomic Investigation of Human Pigmentation

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Transcriptomic Investigation of Human Pigmentation
Haltaufderhyde, Kirk (creator)
Oancea, Elena (Director)
Morrow, Eric (Reader)
Bowen, Wayne (Reader)
Zimmerman, Anita (Reader)
Dell’Angelica, Esteban (Reader)
Brown University. BIOMED: Molecular Pharmacology, Physiology, and Biotechnology (sponsor)
Copyright Date
We performed a comparative transcriptomic analysis of lightly versus darkly pigmented human epidermal melanocytes (HEMs) using high throughput RNA sequencing (RNA-Seq). We identified 16 genes expressed at significantly different levels between the two pigmentation phenotypes. SLC45A2 was the only pigmentation gene found to be significantly different, leaving 15 novel genes. In addition, we found 166 isoforms that are potentially related to differences in pigmentation. We also analyzed receptor, ion channel and transcription factor gene families to obtain a better understanding of the cell signalling pathways used by melanocytes. Overall, this study provides an updated and comprehensive view of the HEM transcriptome and a foundation for discovering treatment for pigmentation disorders and melanoma. The results of our transcriptome analysis sparked interest in SLC45A2 and its L374F polymorphism. Our investigation of SLC45A2 and the L374F polymorphism determined that both the 374L and 374F isoforms of SLC45A2 localize to melanosomes in melanocytes and to late endosomes and lysosomes when expressed in non-melanocytes. This analysis brings clarity to the localization of SLC45A2 and insight into its function. We also provide the first evidence that the L374F polymorphism can partially rescue melanin content in underwhite cells. Altogether, this study helps to advance our understanding of SLC45A2 and its role in human pigmentation. To better understand the role of opsins in human skin, we also performed a comprehensive analysis of opsin expression in the two major human epidermal cell types, melanocytes and keratinocytes. We demonstrated that OPN1-SW, OPN2, OPN3, and OPN5 are expressed in human epidermal cells. We identified novel splicing isoforms of OPN3 and OPN5 that may play an important regulatory role. The detection of opsins in skin suggests that they function as epidermal photoreceptors, prompting additional studies that will reveal their exact physiological roles. Interestingly, we also identified the expression of opsins in cells not directly exposed to light suggesting possible alternative mechanisms of activation apart from phototransduction.
Human skin color
Thesis (Ph.D. -- Brown University (2015)
xvii, 148 p.


Haltaufderhyde, Kirk, "Transcriptomic Investigation of Human Pigmentation" (2015). Molecular Pharmacology, Physiology, and Biotechnology Theses and Dissertations. Brown Digital Repository. Brown University Library.