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定义膀胱和肾成纤维细胞的分子指纹图谱。

Defining the molecular fingerprint of bladder and kidney fibroblasts.

机构信息

Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States.

出版信息

Am J Physiol Renal Physiol. 2023 Dec 1;325(6):F826-F856. doi: 10.1152/ajprenal.00284.2023. Epub 2023 Oct 12.

Abstract

Fibroblasts are integral to the organization and function of all organs and play critical roles in pathologies such as fibrosis; however, we have limited understanding of the fibroblasts that populate the bladder and kidney. In this review, I describe how transcriptomics is leading to a revolution in our understanding of fibroblast biology by defining the molecular fingerprint (i.e., transcriptome) of universal and specialized fibroblast types, revealing gene signatures that allows one to resolve fibroblasts from other mesenchymal cell types, and providing a new comprehension of the fibroblast lineage. In the kidney, transcriptomics is giving us new insights into the molecular fingerprint of kidney fibroblasts, including those for cortical fibroblasts, medullary fibroblasts, and erythropoietin (EPO)-producing Norn fibroblasts, as well as new information about the gene signatures of kidney myofibroblasts and the transition of kidney fibroblasts into myofibroblasts. Transcriptomics has also revealed that the major cell type in the bladder interstitium is the fibroblast, and that multiple fibroblast types, each with their own molecular fingerprint, are found in the bladder wall. Interleaved throughout is a discussion of how transcriptomics can drive our future understanding of fibroblast identification, diversity, function, and their roles in bladder and kidney biology and physiology in health and in disease states.

摘要

成纤维细胞是所有器官的组织和功能的重要组成部分,并在纤维化等病理学中发挥关键作用;然而,我们对填充在膀胱和肾脏中的成纤维细胞的了解有限。在这篇综述中,我描述了转录组学如何通过定义普遍和特化成纤维细胞类型的分子指纹(即转录组)来引领我们对成纤维细胞生物学理解的革命,揭示了能够将成纤维细胞与其他间充质细胞类型区分开来的基因特征,并提供了对成纤维细胞谱系的新认识。在肾脏中,转录组学为我们提供了对肾脏成纤维细胞分子指纹的新见解,包括皮质成纤维细胞、髓质成纤维细胞和产生促红细胞生成素 (EPO) 的诺恩成纤维细胞,以及关于肾脏肌成纤维细胞的基因特征和肾脏成纤维细胞向肌成纤维细胞转化的新信息。转录组学还揭示了膀胱间质中的主要细胞类型是成纤维细胞,并且在膀胱壁中发现了多种具有各自分子指纹的成纤维细胞类型。贯穿始终的是讨论转录组学如何推动我们未来对成纤维细胞鉴定、多样性、功能及其在膀胱和肾脏生物学和生理学中的作用的理解,包括在健康和疾病状态下的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4173/10886799/6eef8d315fc3/f-00284-2023r01.jpg

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