亲爱的研友该休息了!由于当前在线用户较少,发布求助请尽量完整的填写文献信息,科研通机器人24小时在线,伴您度过漫漫科研夜!身体可是革命的本钱,早点休息,好梦!

Spatial transcriptomic analysis deciphers adipocyte-to-fibroblast transformation in bleomycin-induced murine skin fibrosis

转录组 纤维化 肌成纤维细胞 成纤维细胞 炎症 生物 体内 博莱霉素 脂肪细胞 发病机制 病理 细胞生物学 癌症研究 医学 免疫学 体外 脂肪组织 基因表达 内分泌学 遗传学 基因 化疗
作者
Shouxin Zhang,Jiahao He,Fangzhou Xie,Shengzhou Shan,Jiaqi Qin,Chuandong Wang,Qingfeng Li,Yun Xie,Bin Fang
出处
期刊:Chinese Medical Journal [Ovid Technologies (Wolters Kluwer)]
标识
DOI:10.1097/cm9.0000000000003219
摘要

Abstract Background: Scleroderma is characterized by inflammation and fibrosis, predominantly occurring in the skin and extending to various parts of the body. The pathophysiology of scleroderma is multifaceted, with the current understanding including endothelial damage, inflammatory cell infiltration, and fibroblast activation in its progression. Nonetheless, the mechanism of cellular interactions and the precise spatial distribution of these cellular events within the fibrotic tissues remain elusive, highlighting a critical gap in our comprehensive understanding of scleroderma’s pathogenesis. Methods: In this study, we administered bleomycin intradermally to the dorsal skin of four individual murine models. Subsequently, skin tissues were harvested at predetermined intervals for comprehensive spatial transcriptomic analysis to determine the spatial dynamics influencing scleroderma pathogenesis. To validate the possible results from bioinformatic analysis, further in vitro and in vivo experiments were conducted. Results: Analysis of the spatial transcriptome revealed significant alterations in cell clusters during the progression of scleroderma. Gene Ontology analysis identified disruptions in lipid metabolism as the disease advanced. Pseudotime analysis provided evidence for a phenotypic transition from adipocytes to fibroblasts. In vitro studies demonstrated increased expression of Col1a1 and α-SMA as the disease progressed. These fibroblasts have been identified as key contributors to the increasing inflammation. Co-culturing TGF-β induced adipocytes with RAW264.7 cells resulted in overexpression of pro-inflammatory cytokines in the RAW264.7 cells. Both in vitro and in vivo experiments confirmed adipocyte loss and fibroblast formation, with transformed fibroblasts showing pronounced pro-inflammatory characteristics, highlighting their crucial role in the disease mechanism. Conclusions: Our study showed the spatial distribution and dynamic alterations of various cell types during scleroderma progression. Crucially, we identified the transformation of adipocytes into fibroblasts as a key factor promoting disease advancement. These emergent fibroblasts intensify inflammation, indicating that research on these cell clusters could reveal key scleroderma mechanisms and guide future therapies.
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
大幅提高文件上传限制,最高150M (2024-4-1)

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
amber发布了新的文献求助10
2秒前
思源应助超脱闲人采纳,获得10
5秒前
妖娃娃发布了新的文献求助100
11秒前
黑香菱完成签到,获得积分10
12秒前
16秒前
黑香菱发布了新的文献求助10
21秒前
科研通AI2S应助科研通管家采纳,获得10
21秒前
科研通AI2S应助科研通管家采纳,获得10
21秒前
杳鸢应助科研通管家采纳,获得10
21秒前
29秒前
uouuo完成签到 ,获得积分10
32秒前
桐桐应助黑香菱采纳,获得10
33秒前
情怀应助liugm采纳,获得30
33秒前
鸣蜩阿六发布了新的文献求助10
36秒前
38秒前
斑鸠津发布了新的文献求助10
43秒前
43秒前
酷波er应助斑鸠津采纳,获得10
47秒前
深情安青应助鸣蜩阿六采纳,获得10
48秒前
liugm发布了新的文献求助30
48秒前
51秒前
兴奋元冬发布了新的文献求助20
52秒前
53秒前
liugm完成签到,获得积分10
54秒前
1分钟前
赎罪完成签到 ,获得积分10
1分钟前
鸣蜩阿六发布了新的文献求助10
1分钟前
金蕊完成签到,获得积分10
1分钟前
SmuA完成签到,获得积分10
1分钟前
樱桃猴子应助LukeLion采纳,获得30
1分钟前
光亮如彤完成签到,获得积分10
1分钟前
ftinscience完成签到 ,获得积分10
1分钟前
七七完成签到,获得积分10
1分钟前
Lynny完成签到 ,获得积分10
1分钟前
lazysheep完成签到,获得积分10
1分钟前
1分钟前
1分钟前
梨炒栗子完成签到 ,获得积分10
1分钟前
SolderOH完成签到,获得积分10
1分钟前
额123没名完成签到 ,获得积分10
2分钟前
高分求助中
The late Devonian Standard Conodont Zonation 2000
Nickel superalloy market size, share, growth, trends, and forecast 2023-2030 2000
The Lali Section: An Excellent Reference Section for Upper - Devonian in South China 1500
Very-high-order BVD Schemes Using β-variable THINC Method 890
Mantiden: Faszinierende Lauerjäger Faszinierende Lauerjäger 800
PraxisRatgeber: Mantiden: Faszinierende Lauerjäger 800
A new species of Coccus (Homoptera: Coccoidea) from Malawi 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 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 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3256828
求助须知:如何正确求助?哪些是违规求助? 2898945
关于积分的说明 8303123
捐赠科研通 2568188
什么是DOI,文献DOI怎么找? 1394905
科研通“疑难数据库(出版商)”最低求助积分说明 652924
邀请新用户注册赠送积分活动 630631