title: Durable pluripotency and haploidy in epiblast stem cells derived from haploid embryonic stem cells in vitro.
abstract: Haploid pluripotent stem cells, such as haploid embryonic stem cells (haESCs), facilitate the genetic study of recessive traits. In vitro, fish haESCs maintain haploidy in both undifferentiated and differentiated states, but whether mammalian haESCs can preserve pluripotency in the haploid state has not been tested. Here, we report that mouse haESCs can differentiate in vitro into haploid epiblast stem cells (haEpiSCs), which maintain an intact haploid genome, unlimited self-renewal potential, and durable pluripotency to differentiate into various tissues in vitro and in vivo. Mechanistically, the maintenance of self-renewal potential depends on the Activin/bFGF pathway. We further show that haEpiSCs can differentiate in vitro into haploid progenitor-like cells. When injected into the cytoplasm of an oocyte, androgenetic haEpiSC (ahaEpiSCs) can support embryonic development until midgestation (E12.5). Together, these results demonstrate durable pluripotency in mouse haESCs and haEpiSCs, as well as the valuable potential of using these haploid pluripotent stem cells in high-throughput genetic screening.
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Shuai
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yukai
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Mingzhu
authors.initials: M
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China Graduate School of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Xuepeng
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China Graduate School of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Lisi
authors.initials: L
authors.lastname: Sang
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China College of Life Sciences, Hunan Normal University, Changsha 410081, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Wan
authors.affiliation: Center for Molecular Systems Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Guanzheng
authors.initials: G
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Tiantian
authors.initials: T
authors.lastname: Gu
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China Graduate School of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Chunjing
authors.initials: C
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China Graduate School of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Teng
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Center for Molecular Systems Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Xiuying
authors.initials: X
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Tianda
authors.initials: T
authors.lastname: Li
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Wang
authors.affiliation: Center for Molecular Systems Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Xiu-Jie
authors.initials: XJ
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Xiao-Yang
authors.initials: XY
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China qzhou@ioz.ac.cn.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D003593:Cytoplasm / Q000378:metabolism; D004171:Diploidy; D047108:Embryonic Development; D005855:Germ Layers / Q000166:cytology*; D006238:Haploidy; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology*; D039904:Pluripotent Stem Cells / Q000166:cytology*
keywords: durable pluripotency; epiblast stem cells; haploid