表达gli1祖细胞矿化池形成了肌腱附着点并具有治疗潜力,这一成果由美国哥伦比亚大学Stavros Thomopoulos研究团队经过不懈努力而取得。这一研究成果发表在2022年12月1日出版的国际学术期刊《细胞-干细胞》上。
研究人员使用单细胞RNA测序来确定小鼠出生后阶段的发育转录组。鉴定了6种常驻细胞类型,包括附着点祖细胞和矿化软骨细胞,以及调控它们的转录因子和时间调控。先前发现了Gli1谱系细胞对小鼠附着点发育和愈合的必要性,研究人员随后在单细胞分辨率检查了它们的转录组,并证明表达Gli1祖细胞的克隆原性和多能性。将Gli1谱系细胞移植到小鼠附着点损伤中可改善其愈合,证明其具有对附着点再生的治疗潜力。
据介绍,附着点是肌腱和骨骼之间的纤维软骨过渡组织,是肌肉到骨骼力传递以产生关节运动所必需的。附着点容易受机械力冲击而受伤,并且无法再生。更好地了解附着点如何发育有利于促进有效疗法的产生以预防病理和促进再生。
附:英文原文
Title: A mineralizing pool of Gli1-expressing progenitors builds the tendon enthesis and demonstrates therapeutic potential
Author: Fei Fang, Yang Xiao, Elazar Zelzer, Kam W. Leong, Stavros Thomopoulos
Issue&Volume: 2022/12/01
Abstract: The enthesis, a fibrocartilaginous transition between tendon and bone, is necessaryfor force transfer from muscle to bone to produce joint motion. The enthesis is proneto injury due to mechanical demands, and it cannot regenerate. A better understandingof how the enthesis develops will lead to more effective therapies to prevent pathologyand promote regeneration. Here, we used single-cell RNA sequencing to define the developmentaltranscriptome of the mouse entheses over postnatal stages. Six resident cell types,including enthesis progenitors and mineralizing chondrocytes, were identified alongwith their transcription factor regulons and temporal regulation. Following the priordiscovery of the necessity of Gli1-lineage cells for mouse enthesis development andhealing, we then examined their transcriptomes at single-cell resolution and demonstratedclonogenicity and multipotency of the Gli1-expressing progenitors. Transplantationof Gli1-lineage cells to mouse enthesis injuries improved healing, demonstrating theirtherapeutic potential for enthesis regeneration.
DOI: 10.1016/j.stem.2022.11.007
Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(22)00454-4
Cell Stem Cell:《细胞—干细胞》,创刊于2007年。隶属于细胞出版社,最新IF:21.464
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