Somatic MIWI2 Hinders Direct Lineage Reprogramming From Fibroblast to Hepatocyte

doi:10.1002/stem.2994

	Somatic MIWI2 Hinders Direct Lineage Reprogramming From Fibroblast to Hepatocyte
	Shi, Xiaojie1 ; Xiao, Zipei1,2,3,4 ; Zonta, Francesco1 ; Wang, Wei1 ; Wan, Yue1,2,4 ; Li, Yu1,2,4 ; Wang, Nan1,2,4 ; Kuang, Yuanyuan1,2,4 ; Du, Mingjuan1 ; Dong, Jian 5; Wang, Ju1 ; Yang, Guang1
	2019-06
发表期刊	STEM CELLS
ISSN	1066-5099
卷号	37 期号:6 页码:803-812
发表状态	已发表
DOI	10.1002/stem.2994
摘要	Remodeling of the gene regulatory network in cells is believed to be a prerequisite for their lineage reprogramming. However, its key regulatory factors are not yet elucidated. In this article, we investigate the role of PIWI proteins and provide evidence that one of them, MIWI2, is elicited during transdifferentiation of fibroblasts into hepatocyte-like cells. In coincidence with the peak expression of MIWI2, we identified the appearance of a unique intermediate epigenetic state characterized by a specific Piwi-interacting RNA (piRNA) profile consisting of 219 novel sequences. Knockout of MIWI2 greatly improved the formation of the induced hepatocytes, whereas overexpression of exogenous MIWI2 completely abolished the stimulated effect. A bioinformatics analysis of piRNA interaction network, followed by experimental validation, revealed the Notch signaling pathway as one of the immediate effectors of MIWI2. Altogether, our results show for the first time that temporal expression of MIWI2 contributes negatively to cell plasticity not only in germline, but also in developed cells, such as mouse fibroblasts. Stem Cells 2019;37:803-812
关键词	PIWI MIWI2 piRNA iHep Transdifferentiation Lineage reprogramming Cell fate conversion
收录类别	SCI ; SCIE
语种	英语
资助项目	Science and Technology Commission of Shanghai Municipality[16DZ1910299]
WOS研究方向	Cell Biology ; Biotechnology & Applied Microbiology ; Oncology ; Hematology
WOS类目	Cell & Tissue Engineering ; Biotechnology & Applied Microbiology ; Oncology ; Cell Biology ; Hematology
WOS记录号	WOS:000474038500011
出版者	WILEY
WOS关键词	PIWI-INTERACTING RNAS ; GERMLINE STEM-CELLS ; PIRNA BIOGENESIS ; LENS REGENERATION ; DIRECT CONVERSION ; PROTEINS ; TRANSDIFFERENTIATION ; DEDIFFERENTIATION ; MECHANISMS ; EXPRESSION
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/61120
专题	免疫化学研究所_特聘教授组_Michael Levitt组免疫化学研究所_特聘教授组_功能筛选实验室免疫化学研究所_特聘教授组_抗体设计学实验室生命科学与技术学院_硕士生生命科学与技术学院_博士生免疫化学研究所_公共科研平台_生物医学大数据平台免疫化学研究所_特聘教授组_张宏恺组
通讯作者	Wang, Ju; Yang, Guang
作者单位	1.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai 201210, Peoples R China 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Shanghai, Peoples R China 4.Univ Chinese Acad Sci, Beijing, Peoples R China 5.Kunming Med Univ, Kunming Canc Hosp, Dept Med Oncol, Kunming, Yunnan, Peoples R China
第一作者单位	免疫化学研究所
通讯作者单位	免疫化学研究所
第一作者的第一单位	免疫化学研究所
推荐引用方式 GB/T 7714	Shi, Xiaojie,Xiao, Zipei,Zonta, Francesco,et al. Somatic MIWI2 Hinders Direct Lineage Reprogramming From Fibroblast to Hepatocyte[J]. STEM CELLS,2019,37(6):803-812.
APA	Shi, Xiaojie.,Xiao, Zipei.,Zonta, Francesco.,Wang, Wei.,Wan, Yue.,...&Yang, Guang.(2019).Somatic MIWI2 Hinders Direct Lineage Reprogramming From Fibroblast to Hepatocyte.STEM CELLS,37(6),803-812.
MLA	Shi, Xiaojie,et al."Somatic MIWI2 Hinders Direct Lineage Reprogramming From Fibroblast to Hepatocyte".STEM CELLS 37.6(2019):803-812.