National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Cell Death Dis. 2013 Jan 17;4(1):e464. doi: 10.1038/cddis.2012.196.
Cell fate decision is a critical step during physiological development when embryonic stem cells commit to either becoming adult stem cells or somatic cells. Recent advances in reprogramming demonstrate that a similar set of transcription factors (TFs), which are important for maintaining the pluripotent state of stem cells, can also reprogram somatic cells to induced pluripotent stem cells (iPSCs). In addition, trans-differentiation, which entails the use of different sets of defined factors, whereby one type of somatic cell can be directly converted into another and even to cell types from different germ layers has become a parallel widely used approach for switching cell fate. All these progresses have provided powerful tools to manipulate cells for basic science and therapeutic purposes. Besides protein-based factors, non-coding RNAs (ncRNAs), particularly microRNAs and long ncRNAs, are also involved in cell fate determination, including maintaining self-renewal of pluripotent stem cells and directing cell lineage. Targeting specific ncRNAs represents an alternative promising approach to optimize cell-based disease modeling and regenerative therapy. Here we focus on recent advances of ncRNAs in cell fate decision, including ncRNA-induced iPSCs and lineage conversion. We also discuss some underlying mechanisms and implications in molecular pathogenesis of human diseases.
细胞命运决定是生理发育过程中的一个关键步骤,在此过程中胚胎干细胞决定成为成体干细胞或体细胞。重编程的最新进展表明,一组相似的转录因子(TFs)对于维持干细胞的多能状态非常重要,它们也可以将体细胞重编程为诱导多能干细胞(iPSCs)。此外,转分化涉及使用不同的定义因子集,其中一种体细胞可以直接转化为另一种,甚至可以转化为来自不同胚层的细胞类型,这已成为一种平行的广泛使用的方法来转换细胞命运。所有这些进展为基础科学和治疗目的提供了操纵细胞的强大工具。除了基于蛋白质的因子外,非编码 RNA(ncRNAs),特别是 microRNAs 和长 ncRNAs,也参与细胞命运决定,包括维持多能干细胞的自我更新和指导细胞谱系。针对特定的 ncRNAs 代表了一种有前途的替代方法,可以优化基于细胞的疾病建模和再生治疗。在这里,我们重点介绍 ncRNAs 在细胞命运决定中的最新进展,包括 ncRNA 诱导的 iPSCs 和谱系转换。我们还讨论了一些在人类疾病的分子发病机制中的潜在机制和意义。