MBNL1 和 RBFOX2 合作建立一个涉及多能干细胞分化的剪接程序。

MBNL1 and RBFOX2 cooperate to establish a splicing programme involved in pluripotent stem cell differentiation.

机构信息

1] CNRS, Institut de Génétique Moléculaire de Montpellier, Montpellier F-34293, France [2] Institute of Genetic Medicine, Newcastle University, Newcastle-upon-Tyne NE1 3BZ, UK [3] Université Montpellier 2, F-34293 Montpellier cedex 5, France [4] Université Montpellier 1, F-34094 Montpellier cedex 5, France [5].

出版信息

Nat Commun. 2013;4:2480. doi: 10.1038/ncomms3480.

DOI:10.1038/ncomms3480

PMID:24048253

Abstract

Reprogramming somatic cells into induced pluripotent stem cells (iPSCs) has provided huge insight into the pathways, mechanisms and transcription factors that control differentiation. Here we use high-throughput RT-PCR technology to take a snapshot of splicing changes in the full spectrum of high- and low-expressed genes during induction of fibroblasts, from several donors, into iPSCs and their subsequent redifferentiation. We uncover a programme of concerted alternative splicing changes involved in late mesoderm differentiation and controlled by key splicing regulators MBNL1 and RBFOX2. These critical splicing adjustments arise early in vertebrate evolution and remain fixed in at least 10 genes (including PLOD2, CLSTN1, ATP2A1, PALM, ITGA6, KIF13A, FMNL3, PPIP5K1, MARK2 and FNIP1), implying that vertebrates require alternative splicing to fully implement the instructions of transcriptional control networks.

摘要

将体细胞重编程为诱导多能干细胞（iPSCs），为控制分化的途径、机制和转录因子提供了巨大的见解。在这里，我们使用高通量 RT-PCR 技术，在从多个供体诱导成纤维细胞成为 iPSCs 及其随后的再分化过程中，对高表达和低表达基因的全谱中的剪接变化进行了快照拍摄。我们发现了一个涉及晚期中胚层分化的协调的选择性剪接变化的方案，该方案由关键的剪接调节剂 MBNL1 和 RBFOX2 控制。这些关键的剪接调整在脊椎动物进化的早期就出现了，并且至少在 10 个基因中（包括 PLOD2、CLSTN1、ATP2A1、PALM、ITGA6、KIF13A、FMNL3、PPIP5K1、MARK2 和 FNIP1）保持固定，这意味着脊椎动物需要选择性剪接来完全实现转录控制网络的指令。