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α6-Integrin alternative splicing: distinct cytoplasmic variants in stem cell fate specification and niche interaction

期刊

STEM CELL RESEARCH & THERAPY
卷 9, 期 -, 页码 -

出版社

BIOMED CENTRAL LTD
DOI: 10.1186/s13287-018-0868-3

关键词

alpha 6-Integrin; Stem cell; Stemness; Niche; Alternative splicing

资金

  1. NIH [HL124076, EY027924]
  2. University of Alabama at Birmingham School of Medicine
  3. China Scholarship Council Predoctoral Fellowship [201706370106]
  4. Fundamental Research Funds for the Central Universities of Central South University [2016zzts144]

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alpha 6-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 alpha 6-containing integrins (alpha 6 beta 1 and alpha 6 beta 4) in the regulation of stem cell properties, lineage-specific differentiation, and niche interaction. a6-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 alpha 6 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 alpha 6-integrin subunit and spatiotemporal expression of alpha 6 cytoplasmic variants in embryonic and adult stem/progenitor cells. We highlight the roles of alpha 6 cytoplasmic variants in stem cell fate decision and niche interaction, and discuss the potential mechanisms involved. Understanding of the distinct functions of alpha 6 splicing variants in stem cell biology may inform the rational design of novel stem cell-based therapies for a range of human diseases.

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