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升高的CD47可以作为老化肌肉干细胞增强再生能力的靶点
作者:小柯机器人 发布时间:2022/11/17 22:00:13

美国斯坦福大学医学院Helen M. Blau和Ermelinda Porpiglia共同合作,近期取得重要工作进展。他们研究发现CD47升高是功能失调的老化肌肉干细胞的标志,可以作为增强老化肌肉再生能力的靶点。相关研究成果2022年11月15日在线发表于《细胞—干细胞》杂志上。

研究人员利用质谱流式技术确定CD47高表达是功能失调MuSC(CD47hi)的标志,其再生能力随着年龄的增长而受损。主流的CD47hi-MuSC亚群通过旁分泌信号环路抑制剩余的功能性CD47lo-MuSC亚群,导致增殖受损。老年MuSC上CD47水平的升高是由U1 snRNA表达的增加引起的,它破坏了选择性多聚腺苷酸化。老年MuSC在再生方面的功能缺陷可以通过吗啉代(morpholino)介导的CD47替代聚腺苷酸化的阻断或抗体阻断凝血酶敏感蛋白(thrombospondin-1)/CD47信号传导来克服,从而导致老年小鼠再生能力的改善,具有治疗意义。

这一研究结果强调了以前未发现的MuSC中CD47水平和功能的年龄依赖性改变,这是衰老中肌肉修复减少的基础。

据介绍,在衰老过程中,骨骼肌力量和再生能力下降,部分原因是肌肉干细胞(MuSC)功能受损,但其潜在机制仍不明确。

附:英文原文

Title: Elevated CD47 is a hallmark of dysfunctional aged muscle stem cells that can be targeted to augment regeneration

Author: Ermelinda Porpiglia, Thach Mai, Peggy Kraft, Colin A. Holbrook, Antoine de Morree, Veronica D. Gonzalez, Keren I. Hilgendorf, Laure Frésard, Angelica Trejo, Sriram Bhimaraju, Peter K. Jackson, Wendy J. Fantl, Helen M. Blau

Issue&Volume: 2022-11-15

Abstract: In aging, skeletal muscle strength and regenerative capacity decline, due in partto functional impairment of muscle stem cells (MuSCs), yet the underlying mechanismsremain elusive. Here, we capitalize on mass cytometry to identify high CD47 expressionas a hallmark of dysfunctional MuSCs (CD47hi) with impaired regenerative capacity that predominate with aging. The prevalent CD47hi MuSC subset suppresses the residual functional CD47lo MuSC subset through a paracrine signaling loop, leading to impaired proliferation.We uncover that elevated CD47 levels on aged MuSCs result from increased U1 snRNAexpression, which disrupts alternative polyadenylation. The deficit in aged MuSC functionin regeneration can be overcome either by morpholino-mediated blockade of CD47 alternativepolyadenylation or antibody blockade of thrombospondin-1/CD47 signaling, leading toimproved regeneration in aged mice, with therapeutic implications. Our findings highlighta previously unrecognized age-dependent alteration in CD47 levels and function inMuSCs, which underlies reduced muscle repair in aging.

DOI: 10.1016/j.stem.2022.10.009

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(22)00427-1

期刊信息

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
官方网址:https://www.cell.com/cell-stem-cell/home
投稿链接:https://www.editorialmanager.com/cell-stem-cell/default.aspx