RNA-Seq和ChIP-Seq鉴定TBX4在人肺成纤维细胞和周细胞中调控的独特和重叠靶基因和通路

IF 2.2 4区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS
Pulmonary Circulation Pub Date : 2025-02-19 eCollection Date: 2025-01-01 DOI:10.1002/pul2.70058
Ying Cai, Ling Yan, Joy D Cogan, Lora K Hedges, Bethany Nunley, Nick Negretti, Jennifer M S Sucre, James West, Eric D Austin, Rizwan Hamid
{"title":"RNA-Seq和ChIP-Seq鉴定TBX4在人肺成纤维细胞和周细胞中调控的独特和重叠靶基因和通路","authors":"Ying Cai, Ling Yan, Joy D Cogan, Lora K Hedges, Bethany Nunley, Nick Negretti, Jennifer M S Sucre, James West, Eric D Austin, Rizwan Hamid","doi":"10.1002/pul2.70058","DOIUrl":null,"url":null,"abstract":"<p><p>Transcription factor <i>TBX4</i> rare variants associate with pulmonary arterial hypertension (PAH), particularly in children, and are the second most common cause of heritable PAH. However, TBX4's down-stream targets and the molecular and cellular pathways these targets regulate remain largely unknown in PAH. We combined RNA-seq and ChIP-seq results to identify TBX4 direct targets in lung fibroblasts and pericytes, respectively. There were 555 genes with altered expression with TBX4 knockdown in both fibroblasts and pericytes by RNA-seq, and which also were found to be bound by TBX4 by ChIP-seq. Gene ontology analysis found that these were dominated by genes related to extracellular matrix, actin organization, and migration guidance, although there were also significant groups related to serine/threonine kinase signaling, GTPase mediated signaling, and glycoprotein metabolism. Migration and proliferation studies using TBX4 knockdown fibroblasts confirmed functional effects. These studies provide the first insights into how genes and pathways regulated by TBX4 are impacted and inform future studies about the key biological processes that lead to PAH in patients who carry pathologic TBX4 rare variants.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"15 1","pages":"e70058"},"PeriodicalIF":2.2000,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11839389/pdf/","citationCount":"0","resultStr":"{\"title\":\"RNA-Seq and ChIP-Seq Identification of Unique and Overlapping Target Genes and Pathways Regulated by TBX4 in Human Pulmonary Fibroblasts and Pericytes.\",\"authors\":\"Ying Cai, Ling Yan, Joy D Cogan, Lora K Hedges, Bethany Nunley, Nick Negretti, Jennifer M S Sucre, James West, Eric D Austin, Rizwan Hamid\",\"doi\":\"10.1002/pul2.70058\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Transcription factor <i>TBX4</i> rare variants associate with pulmonary arterial hypertension (PAH), particularly in children, and are the second most common cause of heritable PAH. However, TBX4's down-stream targets and the molecular and cellular pathways these targets regulate remain largely unknown in PAH. We combined RNA-seq and ChIP-seq results to identify TBX4 direct targets in lung fibroblasts and pericytes, respectively. There were 555 genes with altered expression with TBX4 knockdown in both fibroblasts and pericytes by RNA-seq, and which also were found to be bound by TBX4 by ChIP-seq. Gene ontology analysis found that these were dominated by genes related to extracellular matrix, actin organization, and migration guidance, although there were also significant groups related to serine/threonine kinase signaling, GTPase mediated signaling, and glycoprotein metabolism. Migration and proliferation studies using TBX4 knockdown fibroblasts confirmed functional effects. These studies provide the first insights into how genes and pathways regulated by TBX4 are impacted and inform future studies about the key biological processes that lead to PAH in patients who carry pathologic TBX4 rare variants.</p>\",\"PeriodicalId\":20927,\"journal\":{\"name\":\"Pulmonary Circulation\",\"volume\":\"15 1\",\"pages\":\"e70058\"},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2025-02-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11839389/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pulmonary Circulation\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1002/pul2.70058\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pulmonary Circulation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/pul2.70058","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
引用次数: 0

摘要

转录因子TBX4罕见变异与肺动脉高压(PAH)相关,特别是在儿童中,是遗传性PAH的第二大常见原因。然而,TBX4的下游靶点以及这些靶点调节的分子和细胞途径在PAH中仍然未知。我们结合RNA-seq和ChIP-seq结果分别鉴定了TBX4在肺成纤维细胞和周细胞中的直接靶点。通过RNA-seq检测,在成纤维细胞和周细胞中有555个TBX4基因表达下调的基因,通过ChIP-seq检测也发现这些基因与TBX4结合。基因本体分析发现,这些基因主要与细胞外基质、肌动蛋白组织和迁移指导相关,尽管也有与丝氨酸/苏氨酸激酶信号传导、GTPase介导的信号传导和糖蛋白代谢相关的显著群。TBX4敲低成纤维细胞的迁移和增殖研究证实了其功能作用。这些研究首次揭示了TBX4调控的基因和途径是如何受到影响的,并为未来有关导致携带病理性TBX4罕见变异的患者发生PAH的关键生物学过程的研究提供了信息。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
RNA-Seq and ChIP-Seq Identification of Unique and Overlapping Target Genes and Pathways Regulated by TBX4 in Human Pulmonary Fibroblasts and Pericytes.

Transcription factor TBX4 rare variants associate with pulmonary arterial hypertension (PAH), particularly in children, and are the second most common cause of heritable PAH. However, TBX4's down-stream targets and the molecular and cellular pathways these targets regulate remain largely unknown in PAH. We combined RNA-seq and ChIP-seq results to identify TBX4 direct targets in lung fibroblasts and pericytes, respectively. There were 555 genes with altered expression with TBX4 knockdown in both fibroblasts and pericytes by RNA-seq, and which also were found to be bound by TBX4 by ChIP-seq. Gene ontology analysis found that these were dominated by genes related to extracellular matrix, actin organization, and migration guidance, although there were also significant groups related to serine/threonine kinase signaling, GTPase mediated signaling, and glycoprotein metabolism. Migration and proliferation studies using TBX4 knockdown fibroblasts confirmed functional effects. These studies provide the first insights into how genes and pathways regulated by TBX4 are impacted and inform future studies about the key biological processes that lead to PAH in patients who carry pathologic TBX4 rare variants.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Pulmonary Circulation
Pulmonary Circulation Medicine-Pulmonary and Respiratory Medicine
CiteScore
4.20
自引率
11.50%
发文量
153
审稿时长
15 weeks
期刊介绍: Pulmonary Circulation''s main goal is to encourage basic, translational, and clinical research by investigators, physician-scientists, and clinicans, in the hope of increasing survival rates for pulmonary hypertension and other pulmonary vascular diseases worldwide, and developing new therapeutic approaches for the diseases. Freely available online, Pulmonary Circulation allows diverse knowledge of research, techniques, and case studies to reach a wide readership of specialists in order to improve patient care and treatment outcomes.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信