Deficiency of microRNA miR-34a expands cell fate potential in pluripotent stem cells

Yong Jin Choi; Chao Po Lin; Davide Risso; Sean Chen; Thomas Aquinas Kim; Meng How Tan; Jin Billy Li; Yalei Wu; Caifu Chen; Zhenyu Xuan; Todd Macfarlan; Weiqun Peng; K. C.Kent Lloyd; Sang Yong Kim; Terence P. Speed; Lin He

doi:10.1126/science.aag1927

Deficiency of microRNA miR-34a expands cell fate potential in pluripotent stem cells

Yong Jin Choi, Chao Po Lin, Davide Risso, Sean Chen, Thomas Aquinas Kim, Meng How Tan, Jin Billy Li, Yalei Wu, Caifu Chen, Zhenyu Xuan, Todd Macfarlan, Weiqun Peng, K. C.Kent Lloyd, Sang Yong Kim, Terence P. Speed, Lin He

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Abstract

Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) efficiently generate all embryonic cell lineages but rarely generate extraembryonic cell types. We found that microRNA miR-34a deficiency expands the developmental potential of mouse pluripotent stem cells, yielding both embryonic and extraembryonic lineages and strongly inducing MuERV-L (MERVL) endogenous retroviruses, similar to what is seen with features of totipotent two-cell blastomeres. miR-34a restricts the acquisition of expanded cell fate potential in pluripotent stem cells, and it represses MERVL expression through transcriptional regulation, at least in part by targeting the transcription factor Gata2. Our studies reveal a complex molecular network that defines and restricts pluripotent developmental potential in cultured ESCs and iPSCs.

Original language	English (US)
Article number	eaag1927
Journal	Science
Volume	355
Issue number	6325
DOIs	https://doi.org/10.1126/science.aag1927
State	Published - Feb 10 2017

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title = "Deficiency of microRNA miR-34a expands cell fate potential in pluripotent stem cells",

abstract = "Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) efficiently generate all embryonic cell lineages but rarely generate extraembryonic cell types. We found that microRNA miR-34a deficiency expands the developmental potential of mouse pluripotent stem cells, yielding both embryonic and extraembryonic lineages and strongly inducing MuERV-L (MERVL) endogenous retroviruses, similar to what is seen with features of totipotent two-cell blastomeres. miR-34a restricts the acquisition of expanded cell fate potential in pluripotent stem cells, and it represses MERVL expression through transcriptional regulation, at least in part by targeting the transcription factor Gata2. Our studies reveal a complex molecular network that defines and restricts pluripotent developmental potential in cultured ESCs and iPSCs.",

author = "Choi, {Yong Jin} and Lin, {Chao Po} and Davide Risso and Sean Chen and Kim, {Thomas Aquinas} and Tan, {Meng How} and Li, {Jin Billy} and Yalei Wu and Caifu Chen and Zhenyu Xuan and Todd Macfarlan and Weiqun Peng and Lloyd, {K. C.Kent} and Kim, {Sang Yong} and Speed, {Terence P.} and Lin He",

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doi = "10.1126/science.aag1927",

language = "English (US)",

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AU - Choi, Yong Jin

AU - Lin, Chao Po

AU - Risso, Davide

AU - Chen, Sean

AU - Kim, Thomas Aquinas

AU - Tan, Meng How

AU - Li, Jin Billy

AU - Wu, Yalei

AU - Chen, Caifu

AU - Xuan, Zhenyu

AU - Macfarlan, Todd

AU - Peng, Weiqun

AU - Lloyd, K. C.Kent

AU - Kim, Sang Yong

AU - Speed, Terence P.

AU - He, Lin

PY - 2017/2/10

Y1 - 2017/2/10

N2 - Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) efficiently generate all embryonic cell lineages but rarely generate extraembryonic cell types. We found that microRNA miR-34a deficiency expands the developmental potential of mouse pluripotent stem cells, yielding both embryonic and extraembryonic lineages and strongly inducing MuERV-L (MERVL) endogenous retroviruses, similar to what is seen with features of totipotent two-cell blastomeres. miR-34a restricts the acquisition of expanded cell fate potential in pluripotent stem cells, and it represses MERVL expression through transcriptional regulation, at least in part by targeting the transcription factor Gata2. Our studies reveal a complex molecular network that defines and restricts pluripotent developmental potential in cultured ESCs and iPSCs.

AB - Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) efficiently generate all embryonic cell lineages but rarely generate extraembryonic cell types. We found that microRNA miR-34a deficiency expands the developmental potential of mouse pluripotent stem cells, yielding both embryonic and extraembryonic lineages and strongly inducing MuERV-L (MERVL) endogenous retroviruses, similar to what is seen with features of totipotent two-cell blastomeres. miR-34a restricts the acquisition of expanded cell fate potential in pluripotent stem cells, and it represses MERVL expression through transcriptional regulation, at least in part by targeting the transcription factor Gata2. Our studies reveal a complex molecular network that defines and restricts pluripotent developmental potential in cultured ESCs and iPSCs.

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Deficiency of microRNA miR-34a expands cell fate potential in pluripotent stem cells

Abstract

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