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	Rbm24 Regulates Alternative Splicing Switch in Embryonic Stem Cell Cardiac Lineage Differentiation
	TAO ZHANG ; Zhang T(张涛) ; YU LIN ; Lin Y(林瑜) ; JING LIU ; ZI GUAN ZHANG ; WEI FU ; LI YAN GUO ; LEI PAN ; XU KONG ; MENG KAI ZHANG ; YING HUA LU ; ZHENG RONG HUANG ; QIANG XIE ; WEI HUA LI ; XIU QIN XU ; Xu XQ(徐秀琴)
	2016-03-28
关键词	Rbm24 Alternative splicing Embryonic stem cell Cardiac RNA binding protein
英文摘要	此项研究打破了此前一贯认为干细胞分化是从通过启动转录因子开始的常规方式，首次证明了RNA结合蛋白Rbm24具有调控和促进干细胞向心肌分化的能力，开拓了干细胞分化调控的视野，并且以此方式可以高效获得心肌细胞，为干细胞再生医学转化提供应用前景。 文章第一作者是课题组的博士后张涛和博士生林瑜。; The transition of embryonic stem cell (ESC) pluripotency to differentiation is accompanied by an expansion of mRNA and proteomic diversity. Post-transcriptional regulation of ESCs is critically governed by cell type-specific splicing. However, little is known about the splicing factors and the molecular mechanisms directing ESC early lineage differentiation. Our study identifies RNA binding motif protein 24 (Rbm24) as a key splicing regulator that plays an essential role in controlling post-transcriptional networks during ESC transition into cardiac differentiation. Using an inducible mouse ESC line in which gene expression could be temporally regulated, we demon- strated that forced expression of Rbm24 in ESCs dramatically induced a switch to cardiac specification. Genome-wide RNA sequencing analysis identified more than 200 Rbm24-regulated alternative splicing events (AS) which occurred in genes essential for the ESC pluripotency or differentiation. Remarkably, AS genes regulated by Rbm24 composed of transcriptional factors,cytoskeleton proteins, and ATPase gene family members which are critical components required for cardiac development and functionality. Furthermore, we show that Rbm24 regulates ESC differentiation by promoting alternative splicing of pluripotency genes. Among the Rbm24-regulated events, Tpm1, an actin filament family gene, was identified to possess ESC/tissue specific isoforms. We demonstrated that these isoforms were functionally distinct and that their exon AS switch was essential for ESC differentiation. Our results suggest that ESC's switching into the differentiation state can be initiated by a tissue-specific splicing regulator, Rbm24. This finding offers a global view on how an RNA binding protein influences ESC lineage differentiation by a splicing-mediated regulatory mechanism.; This work was supported by the National Natural Science Foundation of China (NSFC) (Grant no. 81270199), the Major State Basic Research Development Program of China (Grant no. 2014CB965101), Xiamen Joint Research Fund for Major Diseases (3502Z20159014), Research Fund of Xiamen Oceanic Administration (14PYY051SF04), the Natural Science Foundation of Guangdong Province (2015A030310008), the Key Science Foundation of Fujian Province (2013D020), and the Natural Science Foundation of Fujian Province (2012D038).
语种	英语
出版者	John Wiley & Sons, Inc.
内容类型	其他
源URL	[http://dx.doi.org/10.1002/stem.2366]
专题	医学院－已发表论文
推荐引用方式 GB/T 7714	TAO ZHANG,Zhang T,YU LIN,et al. Rbm24 Regulates Alternative Splicing Switch in Embryonic Stem Cell Cardiac Lineage Differentiation. 2016-03-28.

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