单核转录基因分析揭示了在再生肌细胞发生过程中肌纤维XBP1的调节电路
Aniket S Joshi1,2, Micah B Castillo3, Meiricris Tomaz da Silva1,2
1Institute of Muscle Biology and Cachexia, University of Houston College of Pharmacy, Houston, TX 77204, USA.
iScience
|December 9, 2024
概括
展开的蛋白质反应 (UPR) 和其关键组成部分X盒结合蛋白1 (XBP1) 对于骨肌肉再生至关重要. 肌肉纤维中的XBP1控制着卫星细胞的丰富性和肌纤维的形成,影响肌肉的修复.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 再生医学是一种再生医学.
背景情况:
- 细胞内膜网膜 (ER) 的压力和未展开的蛋白质反应 (UPR) 与骨肌肉功能障碍有关.
- 在骨肌肉再生中UPR的具体作用尚不清楚.
研究的目的:
- 研究UPR,特别是X盒结合蛋白1 (XBP1) 在骨肌肉再生中的作用.
- 阐明XBP1在肌肉修复过程中影响肌细胞和非肌细胞的机制.
主要方法:
- 在再生肌肉细胞中诱导UPR标记物.
- 在成年老鼠肌纤维中,XBP1的遗传切除.
- 单核RNA测序 (snRNA-seq) 用于细胞和分子分析.
- 轨迹分析以评估细胞命运和分化.
主要成果:
- 在肌肉再生过程中,肌源性和非肌源性细胞中的UPR标记物都受到上调.
- 在肌纤维中XBP1缺失会损害成年小鼠的肌肉再生.
- 缺少XBP1会影响肌体细胞中的蛋白质溶解系统和线粒体功能.
- XBP1调节卫星细胞的丰富性和肌纤维的形成.
- 切除XBP1会改变受伤肌肉微环境的细胞组成.
结论:
- 肌纤维特定的XBP1对于有效的骨肌肉再生至关重要.
- XBP1通过细胞自主和非自主机制调解肌肉修复.
- 准XBP1通路可能为肌肉再生障碍提供治疗策略.
相关概念视频
Formation of Muscle Fibers from Myoblasts
4.8K
De novo myogenesis, or the formation of muscle fibers, begins during the early embryonic stages. The skeletal muscle is formed from somites– blocks of embryonic cell layers. The somites are further divided into dermatomes, myotomes, sclerotomes, and syndetomes. Among these, the myotomes give rise to muscle fibers.
Muscle progenitor cells (MPCs) are formed from the myotomes. MPCs express genes that encode the transcription factors Pax3 and Pax7. Along with Pax 3/7, other transcription...
Muscle progenitor cells (MPCs) are formed from the myotomes. MPCs express genes that encode the transcription factors Pax3 and Pax7. Along with Pax 3/7, other transcription...
4.8K
Master Transcription Regulators
6.9K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.9K
Satellite Stem Cells and Muscular Dystrophy
1.9K
Satellite stem cells or myosatellite cells are quiescent stem cells that Alexander Mauro first identified in 1961. These cells are located between the sarcolemma, the plasma membrane of muscle fibers, and the basal lamina, the connective tissue sheath covering it. These mononucleated cells are activated in response to muscle injury, can transform into myoblasts, and may form or repair muscle fibers. Myosatellite cells can provide additional myonuclei for muscle regeneration or return to a...
1.9K
Cross-bridge Cycle
116.9K
As muscle contracts, the overlap between the thin and thick filaments increases, decreasing the length of the sarcomere—the contractile unit of the muscle—using energy in the form of ATP. At the molecular level, this is a cyclic, multistep process that involves binding and hydrolysis of ATP, and movement of actin by myosin.
116.9K
TGF - β Signaling Pathway
7.2K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.2K


