title: Dynamic transcriptional symmetry-breaking in pre-implantation mammalian embryo development revealed by single-cell RNA-seq.
abstract: During mammalian pre-implantation embryo development, when the first asymmetry emerges and how it develops to direct distinct cell fates remain longstanding questions. Here, by analyzing single-blastomere transcriptome data from mouse and human pre-implantation embryos, we revealed that the initial blastomere-to-blastomere biases emerge as early as the first embryonic cleavage division, following a binomial distribution pattern. The subsequent zygotic transcriptional activation further elevated overall blastomere-to-blastomere biases during the two- to 16-cell embryo stages. The trends of transcriptional asymmetry fell into two distinct patterns: for some genes, the extent of asymmetry was minimized between blastomeres (monostable pattern), whereas other genes, including those known to be lineage specifiers, showed ever-increasing asymmetry between blastomeres (bistable pattern), supposedly controlled by negative or positive feedbacks. Moreover, our analysis supports a scenario in which opposing lineage specifiers within an early blastomere constantly compete with each other based on their relative ratio, forming an inclined 'lineage strength' that pushes the blastomere onto a predisposed, yet flexible, lineage track before morphological distinction.
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, 100101 Beijing, China University of Chinese Academy of Sciences, 100049 Beijing, China.
authors.forename: Junchao
authors.initials: J
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, 100101 Beijing, China Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA cqi@medicine.nevada.edu yitao@ioz.ac.cn qzhou@ioz.ac.cn duane@ioz.ac.cn.
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, 100101 Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, 100101 Beijing, China.
authors.forename: Xiudeng
authors.initials: X
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, 100101 Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Biodynamic Optical Imaging Center and Center for Reproductive Medicine, College of Life Sciences, Third Hospital, Peking University, 100871 Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Qiao
authors.affiliation: Biodynamic Optical Imaging Center and Center for Reproductive Medicine, College of Life Sciences, Third Hospital, Peking University, 100871 Beijing, China.
authors.forename: Fuchou
authors.initials: F
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, 100101 Beijing, China cqi@medicine.nevada.edu yitao@ioz.ac.cn qzhou@ioz.ac.cn duane@ioz.ac.cn.
authors.forename: Yi
authors.initials: Y
authors.lastname: Tao
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, 100101 Beijing, China cqi@medicine.nevada.edu yitao@ioz.ac.cn qzhou@ioz.ac.cn duane@ioz.ac.cn.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, 100101 Beijing, China cqi@medicine.nevada.edu yitao@ioz.ac.cn qzhou@ioz.ac.cn duane@ioz.ac.cn.
authors.forename: Enkui
authors.initials: E
authors.lastname: Duan
mesh_terms: D000818:Animals; D001755:Blastocyst; D001757:Blastomeres / Q000502:physiology*; D019521:Body Patterning; D000071616:CDX2 Transcription Factor; D019070:Cell Lineage; D016000:Cluster Analysis; D010064:Embryo Implantation; D004622:Embryo, Mammalian; D047108:Embryonic Development; D005260:Female; D018398:Homeodomain Proteins / Q000502:physiology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D011484:Protein-Arginine N-Methyltransferases / Q000502:physiology; D012313:RNA / Q000032:analysis; D017423:Sequence Analysis, RNA / Q000379:methods*; D059010:Single-Cell Analysis; D013997:Time Factors; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D015053:Zygote / Q000502:physiology
chemical_list: D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; C487514:Cdx2 protein, mouse; D018398:Homeodomain Proteins; D014157:Transcription Factors; D012313:RNA; D011484:Protein-Arginine N-Methyltransferases; C119966:coactivator-associated arginine methyltransferase 1
keywords: Bistable model; Lineage divergence; Monostable model; Pre-implantation embryo development; Transcriptional symmetry-breaking