Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Tinsley Harrison Tower 437B, 1900 University Blvd, Birmingham, AL, 35294, USA.
Department of Respiratory Medicine, The Second Xiangya Hospital, Central-South University, Changsha, 410011, Hunan, China.
Stem Cell Res Ther. 2018 May 2;9(1):122. doi: 10.1186/s13287-018-0868-3.
α6-Integrin subunit (also known as CD49f) is a stemness signature that has been found on the plasma membrane of more than 30 stem cell populations. A growing body of studies have focused on the critical role of α6-containing integrins (α6β1 and α6β4) in the regulation of stem cell properties, lineage-specific differentiation, and niche interaction. α6-Integrin subunit can be alternatively spliced at the post-transcriptional level, giving rise to divergent isoforms which differ in the cytoplasmic and/or extracellular domains. The cytoplasmic domain of integrins is an important functional part of integrin-mediated signals. Structural changes in the cytoplasmic domain of α6 provide an efficient means for the regulation of stem cell responses to biochemical stimuli and/or biophysical cues in the stem cell niche, thus impacting stem cell fate determination. In this review, we summarize the current knowledge on the structural variants of the α6-integrin subunit and spatiotemporal expression of α6 cytoplasmic variants in embryonic and adult stem/progenitor cells. We highlight the roles of α6 cytoplasmic variants in stem cell fate decision and niche interaction, and discuss the potential mechanisms involved. Understanding of the distinct functions of α6 splicing variants in stem cell biology may inform the rational design of novel stem cell-based therapies for a range of human diseases.
α6-整合素亚基（也称为 CD49f）是一种干性特征标志物，已在 30 多种干细胞群体的质膜上发现。越来越多的研究集中在含有α6 的整合素（α6β1 和 α6β4）在调节干细胞特性、谱系特异性分化和生态位相互作用中的关键作用。α6-整合素亚基可以在转录后水平进行选择性剪接，产生不同的亚型，在细胞质和/或细胞外结构域上存在差异。整合素的细胞质结构域是整合素介导信号的重要功能部分。α6 细胞质结构域的结构变化为调节干细胞对干细胞生态位中的生化刺激和/或生物物理线索的反应提供了一种有效的手段，从而影响干细胞命运决定。在这篇综述中，我们总结了 α6-整合素亚基的结构变体以及在胚胎和成体干细胞/祖细胞中的时空表达的最新知识。我们强调了 α6 细胞质变体在干细胞命运决定和生态位相互作用中的作用，并讨论了所涉及的潜在机制。了解 α6 剪接变体在干细胞生物学中的不同功能可能为一系列人类疾病的新型基于干细胞的治疗提供合理的设计。
