Transcriptome analysis of PDGFRα+ cells identifies T-type Ca2+ channel CACNA1G as a new pathological marker for PDGFRα+ cell hyperplasia

Se Eun Ha; Moon Young Lee; Masaaki Kurahashi; Lai Wei; Brian G Jorgensen; Chanjae Park; Paul J Park; Doug Redelman; Kent C Sasse; Laren S Becker; Kenton M Sanders; Seungil Ro

doi:10.1371/journal.pone.0182265

Back

Transcriptome analysis of PDGFRα+ cells identifies T-type Ca2+ channel CACNA1G as a new pathological marker for PDGFRα+ cell hyperplasia

Journal article

Open access

Peer reviewed

Transcriptome analysis of PDGFRα+ cells identifies T-type Ca2+ channel CACNA1G as a new pathological marker for PDGFRα+ cell hyperplasia

Se Eun Ha, Moon Young Lee, Masaaki Kurahashi, Lai Wei, Brian G Jorgensen, Chanjae Park, Paul J Park, Doug Redelman, Kent C Sasse, Laren S Becker, …

PloS one, Vol.12(8), pp.e0182265-e0182265

2017

DOI: 10.1371/journal.pone.0182265

PMCID: PMC5555714

PMID: 28806761

Files and links (1)

url

https://doi.org/10.1371/journal.pone.0182265View

Published (Version of record) Open Access

Abstract

Platelet-derived growth factor receptor alpha (PDGFRα)+ cells are distributed into distinct morphological groups within the serosal, muscular, and submucosal layers as well as the myenteric and deep muscular plexi. PDGFRα+ cells directly interact with interstitial cells of Cajal (ICC) and smooth muscle cells (SMC) in gastrointestinal smooth muscle tissue. These three cell types, SMC, ICC, and PDGFRα+ cells (SIP cells), form an electrical syncytium, which dynamically regulates gastrointestinal motility. We have previously reported the transcriptomes of SMC and ICC. To complete the SIP cell transcriptome project, we obtained transcriptome data from jejunal and colonic PDGFRα+ cells. The PDGFRα+ cell transcriptome data were added to the Smooth Muscle Genome Browser that we previously built for the genome-scale gene expression data of ICC and SMC. This browser provides a comprehensive reference for all transcripts expressed in SIP cells. By analyzing the transcriptomes, we have identified a unique set of PDGFRα+ cell signature genes, growth factors, transcription factors, epigenetic enzymes/regulators, receptors, protein kinases/phosphatases, and ion channels/transporters. We demonstrated that the low voltage-dependent T-type Ca2+ channel Cacna1g gene was particularly expressed in PDGFRα+ cells in the intestinal serosal layer in mice. Expression of this gene was significantly induced in the hyperplasic PDGFRα+ cells of obstructed small intestine in mice. This gene was also over-expressed in colorectal cancer, Crohn's disease, and diverticulitis in human patients. Taken together, our data suggest that Cacna1g exclusively expressed in serosal PDGFRα+ cells is a new pathological marker for gastrointestinal diseases.

Animals

Calcium Channels, T-Type - genetics

Calcium Channels, T-Type - metabolism

Cell Dedifferentiation

Cell Proliferation - genetics

Cell Separation

Gene Expression Profiling

Gene Expression Regulation

Genome

Humans

Hyperplasia

Hypertrophy

Ion Channels - genetics

Ion Channels - metabolism

Jejunum - metabolism

Mice

Muscle, Smooth - metabolism

Protein Isoforms - genetics

Protein Isoforms - metabolism

Receptor, Platelet-Derived Growth Factor alpha - metabolism

RNA, Messenger - genetics

RNA, Messenger - metabolism

Details

Title: Subtitle: Transcriptome analysis of PDGFRα+ cells identifies T-type Ca2+ channel CACNA1G as a new pathological marker for PDGFRα+ cell hyperplasia
Creators: Se Eun Ha - University of Nevada, Reno
Moon Young Lee - Wonkwang University
Masaaki Kurahashi - University of Nevada, Reno
Lai Wei - University of Nevada, Reno
Brian G Jorgensen - University of Nevada, Reno
Chanjae Park - University of Nevada, Reno
Paul J Park - University of Nevada, Reno
Doug Redelman - University of Nevada, Reno
Kent C Sasse - Sasse Surgical Associates, Reno, Nevada, United States of America.
Laren S Becker - Stanford University
Kenton M Sanders - University of Nevada, Reno
Seungil Ro - University of Nevada, Reno
Resource Type: Journal article
Publication Details: PloS one, Vol.12(8), pp.e0182265-e0182265
DOI: 10.1371/journal.pone.0182265
PMID: 28806761
PMCID: PMC5555714
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Grant note: R01 DK094886 / NIDDK NIH HHS P01 DK041315 / NIDDK NIH HHS R01 DK103055 / NIDDK NIH HHS R01 DK091336 / NIDDK NIH HHS
Language: English
Date published: 2017
Academic Unit: Internal Medicine
Record Identifier: 9984359570902771

Metrics

6 Record Views

32 Times Cited - Web of Science

See more details