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.
Highlights
In the gastrointestinal (GI) tract, enteric motor neurons coordinate contractile behavior to create productive motor patterns smooth muscles autonomously generate rhythmic contractile activity independent of neuronal input [1, 2]
We sorted PDGFRα+ cells (PαC) from 30 mice on the basis of eGFP by fluorescence-activated cell sorting (FACS), pooled them according to tissue of origin, and isolated mRNAs from each of the two groups of cells
The transcriptomes include all gene isoforms and splice variants expressed in SIP cells (SMC, interstitial cells of Cajal (ICC), and PαC) isolated from the murine jejunum and colon
Summary
In the gastrointestinal (GI) tract, enteric motor neurons coordinate contractile behavior to create productive motor patterns smooth muscles autonomously generate rhythmic contractile activity independent of neuronal input [1, 2]. Autonomous motor activity and neural regulation are achieved through the integrated activities and responses of smooth muscle cells (SMC), interstitial cells of Cajal (ICC), and platelet-derived growth factor receptor alpha (PDGFRα)+ cells (PαC). These cells form an electrical syncytium, collectively known as the SIP (SMC, ICC, and PαC) syncytium. ICC and PαC are localized in similar anatomical niches in the serosal, myenteric, intramuscular, and submucosal regions of GI muscles [5, 6] Both types of interstitial cells, ICC and PαC, are closely associated with enteric neurons and electrically coupled to SMC [5]. Due to the coupling of Ca2+-activated Cl- channels to Ca2+ release events in ICC [12,13,14] and coupling of SK3 channels to Ca2+-release events in PαC [11, 15, 16], stimuli initiating Ca2+ release in these cells will have opposite effects on the excitability of the SIP syncytium: Ca2+ mobilization in ICC and PαC will exert excitatory and inhibitory effects on the SMC component of the SIP syncytium
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