Spatial and single-cell transcriptomics reveal the regional division of the spatial structure of NASH fibrosis

纤维化 生物 转录组 肌成纤维细胞 旁分泌信号 细胞 细胞生物学 计算生物学 基因 病理 基因表达 受体 遗传学 医学
作者
Min‐ran Li,Jinzhong Li,Lihong Ye,Li Ni,Xin Huang,Xujing Liang,Hai-cong Zhang,Zhiquan Liu,Xuedong Zhang,Junqing Li,Mingkai Chen,Tao-yuan Li,Yang Liu,Jieying Li,Yang Cao,Yun Pan,Xun-ge Lin,Calvin Q. Pan,Erhei Dai,Min‐ran Li
出处
期刊:Research Square - Research Square 被引量:2
标识
DOI:10.21203/rs.3.rs-2958625/v1
摘要

Abstract Objective : To reveal the regional division of the spatial structure of NASH fibrosis and the communication relationship between cells in different regions and to analyse specific marker genes as potential therapeutic targets for NASH fibrosis. Methods: The liver sections of healthy controls, NAFL patients and NASH patients were measured by spatial transcriptomics, and integration analysis was performed with single-cell RNA-seq. Differential expression, functional pathway prediction, and deconvolution analysis revealed lineage-specific changes in gene expression, subpopulation composition and intercellular communication in NASH and identified key genes involved in HSC activation. The role of key genes in NASH fibrosis was verified in vitro and in vivo. Result : Descending and clustering analysis of 4114 nuclei from liver tissues of healthy controls, NAFL, and NASH showed that the distribution of cluster5 (fibrotic region) is dominated by lobules, and a small amount of fibrosis can be seen in the sink area. Functional analysis suggested that differentially expressed genes of cluster5 were concentrated in ECM structural components and signalling molecules. Six cell types were obtained by integrating the single-cell sequencing dataset (GSE189175). Compared with the healthy control and NAFL groups, the NASH group had significantly increased proportions of HSCs and myofibroblasts, which were distributed in the lobule and the portal area around the fibrotic area. Simultaneously, the infiltration of Kupffer cells around the fibrotic area also increased. The cell communication analysis showed that diffusive cell communication was the main type, including endocrine, paracrine and autocrine communication, followed by ECM-receptor cell communication. According to the analysis of differentially expressed genes in the subsets, AEBP1 and DPT are relatively highly expressed in cluster5, as well as in HSCs and myofibroblasts. SCENIC analysis found that AEBP1+ and DPT+ myoblasts were involved in the activation of HSCs and fibrosis formation. Immunohistochemistry verified the high expression of AEBP1 and DPT in patients with NASH fibrosis. After transfection of AEBP1 and DPT interference fragments in LX2 cells in vitro, the mRNA level of Collagen Ⅰ in cells was significantly lower than that of the siRNA-NC group and blank control group. Conclusion: Our study is the first to reveal lineage-specific changes in gene expression, subpopulation composition and cell communication in NASH fibrosis, providing new directions for potential therapeutic targets for NASH fibrosis.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
桔子完成签到,获得积分10
1秒前
二般人完成签到 ,获得积分10
6秒前
忐忑的阑香完成签到,获得积分10
7秒前
7秒前
罗晓倩完成签到,获得积分10
7秒前
ShiyuZuo完成签到,获得积分10
8秒前
诚心千筹发布了新的文献求助10
11秒前
11秒前
YamDaamCaa应助shawn采纳,获得100
14秒前
桃子完成签到,获得积分20
14秒前
Rondab应助大观天下采纳,获得30
15秒前
DijiaXu应助爱科研采纳,获得10
18秒前
水中鱼完成签到,获得积分10
18秒前
共享精神应助无情的匪采纳,获得10
18秒前
科目三应助yoyo采纳,获得10
18秒前
19秒前
前隆是狗完成签到,获得积分10
19秒前
yyyyyyy111发布了新的文献求助10
22秒前
SYLH应助淅淅12345采纳,获得10
23秒前
25秒前
YWang发布了新的文献求助10
26秒前
李健的小迷弟应助hh采纳,获得10
27秒前
29秒前
Orange应助莉丽采纳,获得10
29秒前
30秒前
juwish完成签到,获得积分10
31秒前
cst发布了新的文献求助10
31秒前
量子星尘发布了新的文献求助10
31秒前
Fengliguantou发布了新的文献求助10
32秒前
32秒前
脑洞疼应助zriverm采纳,获得10
33秒前
林宝雯发布了新的文献求助10
34秒前
cccyq完成签到,获得积分10
35秒前
36秒前
诚心千筹完成签到,获得积分10
37秒前
38秒前
pppp完成签到,获得积分10
39秒前
40秒前
情怀应助YWang采纳,获得10
41秒前
香蕉梨愁完成签到,获得积分10
42秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
‘Unruly’ Children: Historical Fieldnotes and Learning Morality in a Taiwan Village (New Departures in Anthropology) 400
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3989069
求助须知:如何正确求助?哪些是违规求助? 3531351
关于积分的说明 11253589
捐赠科研通 3269939
什么是DOI,文献DOI怎么找? 1804851
邀请新用户注册赠送积分活动 882074
科研通“疑难数据库(出版商)”最低求助积分说明 809073