Title Information
Title
Transcriptomic Investigation of Human Pigmentation
Name: Personal
Name Part
Haltaufderhyde, Kirk
Role
Role Term: Text
creator
Origin Information
Copyright Date
2015
Physical Description
Extent
xvii, 148 p.
digitalOrigin
born digital
Note
Thesis (Ph.D. -- Brown University (2015)
Name: Personal
Name Part
Oancea, Elena
Role
Role Term: Text
Director
Name: Personal
Name Part
Morrow, Eric
Role
Role Term: Text
Reader
Name: Personal
Name Part
Bowen, Wayne
Role
Role Term: Text
Reader
Name: Personal
Name Part
Zimmerman, Anita
Role
Role Term: Text
Reader
Name: Personal
Name Part
Dell’Angelica, Esteban
Role
Role Term: Text
Reader
Name: Corporate
Name Part
Brown University. BIOMED: Molecular Pharmacology, Physiology, and Biotechnology
Role
Role Term: Text
sponsor
Type of Resource
text
Genre (aat)
theses
Abstract
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.
Subject
Topic
pigmentation
Subject
Topic
SLC45A2
Subject
Topic
opsins
Subject (FAST) (authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/1120047")
Topic
Skin
Subject (FAST) (authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/963464")
Topic
Human skin color
Subject (FAST) (authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/1015684")
Topic
Melanocytes
Subject (FAST) (authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/1015679")
Topic
Melanins
Record Information
Record Content Source (marcorg)
RPB
Record Creation Date (encoding="iso8601")
20150601
Language
Language Term: Code (ISO639-2B)
eng
Language Term: Text
English
Identifier: DOI
10.7301/Z0RV0M2V