Transcriptome analysis of PDGFRα+ cells identifies T-type Ca2+ channel CACNA1G as a new pathological marker for PDGFRα+ cell hyperplasia.
Transcriptome analysis of PDGFRα+ cells identifies T-type Ca2+ channel CACNA1G as a new pathological marker for PDGFRα+ cell hyperplasia.
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DOI：
10.1371/journal.pone.0182265
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Ro S
中科院分区：
文献类型：
--
作者：
Ha SE;Lee MY;Kurahashi M;Wei L;Jorgensen BG;Park C;Park PJ;Redelman D;Sasse KC;Becker LS;Sanders KM;Ro S
血小板衍生生长因子受体α(PDGFRα)阳性细胞在浆膜层、肌层、粘膜下层以及肌间神经丛和深层肌丛中分布有不同的形态群。PDGFRα+细胞与胃肠道平滑肌组织中的卡哈尔间质细胞和平滑肌细胞直接相互作用。这三种细胞类型，即SMC、ICC和PDGFRα+细胞(SIPcell)，形成一个电子合胞体，动态调节胃肠运动。我们之前已经报道了SMC和ICC的转录本。为了完成细胞转录组计划，我们获得了空肠和结肠PDGFRα+细胞的转录组数据。将PDGFRα+细胞转录组数据添加到我们先前为血管内皮细胞和平滑肌细胞基因组级基因表达数据构建的平滑肌基因组浏览器中。该浏览器为所有在SIP细胞中表达的转录本提供了全面的参考。通过对转录本的分析，我们已经确定了一组独特的PDGFRα+细胞特征基因、生长因子、转录因子、表观遗传酶/调节因子、受体、蛋白激酶/磷酸酶和离子通道/转运体。我们证明了低电压依赖性T型钙通道CacNA1g基因在小鼠肠道浆膜层的PDGFRα+细胞中特异表达。该基因在梗阻小鼠小肠α+细胞中的表达明显增强。该基因在人类患者的结直肠癌、克罗恩病和憩室炎中也过度表达。综上所述，我们的数据表明，CacNA1g仅在血清PDGFRα+细胞中表达，是一种新的胃肠道疾病的病理标志物。
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.
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影响因子：
25
作者：
Li S;Nie EH;Yin Y;Benowitz LI;Tung S;Vinters HV;Bahjat FR;Stenzel-Poore MP;Kawaguchi R;Coppola G;Carmichael ST
通讯作者：
Carmichael ST
影响因子：
5.2
作者：
Dziegielewska, Barbara;Brautigan, David L.;Dziegielewski, Jaroslaw
通讯作者：
Dziegielewski, Jaroslaw
影响因子：
4
作者：
Lu, Fengmin;Chen, Hairu;Wu, Songwei
通讯作者：
Wu, Songwei
DOI：
10.1073/pnas.86.18.7280
发表时间：
1989-09-01
影响因子：
11.1
作者：
LANGTON, P;WARD, SM;SANDERS, KM
通讯作者：
SANDERS, KM
DOI：
10.1016/s0165-1838(00)00089-8
发表时间：
2000-05-12
期刊：
JOURNAL OF THE AUTONOMIC NERVOUS SYSTEM
影响因子：
--
作者：
Horiguchi, K;Komuro, T
通讯作者：
Komuro, T