title: Genetic programs in human and mouse early embryos revealed by single-cell RNA sequencing.
abstract: Mammalian pre-implantation development is a complex process involving dramatic changes in the transcriptional architecture. We report here a comprehensive analysis of transcriptome dynamics from oocyte to morula in both human and mouse embryos, using single-cell RNA sequencing. Based on single-nucleotide variants in human blastomere messenger RNAs and paternal-specific single-nucleotide polymorphisms, we identify novel stage-specific monoallelic expression patterns for a significant portion of polymorphic gene transcripts (25 to 53%). By weighted gene co-expression network analysis, we find that each developmental stage can be delineated concisely by a small number of functional modules of co-expressed genes. This result indicates a sequential order of transcriptional changes in pathways of cell cycle, gene regulation, translation and metabolism, acting in a step-wise fashion from cleavage to morula. Cross-species comparisons with mouse pre-implantation embryos reveal that the majority of human stage-specific modules (7 out of 9) are notably preserved, but developmental specificity and timing differ between human and mouse. Furthermore, we identify conserved key members (or hub genes) of the human and mouse networks. These genes represent novel candidates that are likely to be key in driving mammalian pre-implantation development. Together, the results provide a valuable resource to dissect gene regulatory mechanisms underlying progressive development of early mammalian embryos.
authors.affiliation: Translational Center for Stem Cell Research, Tongji Hospital, Department of Regenerative Medicine, Tongji University School of Medicine, Shanghai 200065, China. xuezhigang75@gmail.com
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Xue
authors.forename: Kevin
authors.initials: K
authors.lastname: Huang
authors.forename: Chaochao
authors.initials: C
authors.lastname: Cai
authors.forename: Lingbo
authors.initials: L
authors.lastname: Cai
authors.forename: Chun-yan
authors.initials: CY
authors.lastname: Jiang
authors.forename: Yun
authors.initials: Y
authors.lastname: Feng
authors.forename: Zhenshan
authors.initials: Z
authors.lastname: Liu
authors.forename: Qiao
authors.initials: Q
authors.lastname: Zeng
authors.forename: Liming
authors.initials: L
authors.lastname: Cheng
authors.forename: Yi E
authors.initials: YE
authors.lastname: Sun
authors.forename: Jia-yin
authors.initials: JY
authors.lastname: Liu
authors.forename: Steve
authors.initials: S
authors.lastname: Horvath
authors.forename: Guoping
authors.initials: G
authors.lastname: Fan
mesh_terms: D000483:Alleles; D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics; D004622:Embryo, Mammalian / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D047108:Embryonic Development / Q000235:genetics*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D009028:Morula / Q000166:cytology / Q000378:metabolism; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D017423:Sequence Analysis, RNA; D059010:Single-Cell Analysis
references.citation: Nat Genet. 2010 Nov;42(11):969-72
references.pmid: 20890277
references.citation: Genome Res. 2010 Sep;20(9):1297-303
references.pmid: 20644199
references.citation: Hum Mol Genet. 2004 Jul 15;13(14):1461-70
references.pmid: 15150160
references.citation: J Biol Chem. 2010 Oct 22;285(43):33113-33122
references.pmid: 20699224
references.citation: Nat Biotechnol. 2012 Aug;30(8):777-82
references.pmid: 22820318
references.citation: PLoS One. 2011;6(6):e21208
references.pmid: 21731673
references.citation: Proc Natl Acad Sci U S A. 2010 Jul 13;107(28):12698-703
references.pmid: 20616000
references.citation: Dev Biol. 2004 Aug 15;272(2):483-96
references.pmid: 15282163
references.citation: Genome Res. 2010 Jun;20(6):804-15
references.pmid: 20219939
references.citation: Bioinformatics. 2009 Jul 15;25(14):1754-60
references.pmid: 19451168
references.citation: Science. 2007 Apr 20;316(5823):406-7
references.pmid: 17446392
references.citation: Dev Cell. 2004 Jan;6(1):133-44
references.pmid: 14723853
references.citation: Cell Rep. 2012 Sep 27;2(3):666-73
references.pmid: 22939981
references.citation: Genome Res. 2011 Jul;21(7):1160-7
references.pmid: 21543516
references.citation: PLoS One. 2009 Nov 16;4(11):e7844
references.pmid: 19924284
references.citation: Nature. 2010 Oct 28;467(7319):1061-73
references.pmid: 20981092
references.citation: BMC Bioinformatics. 2004 Feb 19;5:17
references.pmid: 15028117
references.citation: PLoS Comput Biol. 2011 Jan 20;7(1):e1001057
references.pmid: 21283776
references.citation: Nat Protoc. 2009;4(1):44-57
references.pmid: 19131956
references.citation: BMC Bioinformatics. 2007 Jan 24;8:22
references.pmid: 17250769
references.citation: Nature. 2010 Sep 2;467(7311):52-8
references.pmid: 20811451
references.citation: Dev Cell. 2004 Jan;6(1):117-31
references.pmid: 14723852
references.citation: Science. 2002 Jun 21;296(5576):2225-9
references.pmid: 12029063
references.citation: Nucleic Acids Res. 2010 Sep;38(16):e164
references.pmid: 20601685
references.citation: Genes Dev. 2005 Jul 1;19(13):1581-95
references.pmid: 15998811
references.citation: Nat Methods. 2008 Jul;5(7):621-8
references.pmid: 18516045
references.citation: Bioinformatics. 2008 Mar 1;24(5):719-20
references.pmid: 18024473
references.citation: Development. 2011 Sep;138(17):3699-709
references.pmid: 21775417
references.citation: Nat Protoc. 2010 Mar;5(3):516-35
references.pmid: 20203668
references.citation: Stat Appl Genet Mol Biol. 2005;4:Article17
references.pmid: 16646834
references.citation: Development. 2012 Mar;139(5):829-41
references.pmid: 22318624
references.citation: Nucleic Acids Res. 2012 Jan;40(Database issue):D881-6
references.pmid: 22075990
references.citation: BMC Bioinformatics. 2008 Dec 29;9:559
references.pmid: 19114008
references.citation: Hum Reprod Update. 2002 Jul-Aug;8(4):323-31
references.pmid: 12206467
references.citation: Nat Protoc. 2009;4(7):1073-81
references.pmid: 19561590
references.citation: Curr Opin Genet Dev. 2011 Aug;21(4):431-43
references.pmid: 21497081
references.citation: PLoS Comput Biol. 2008 Aug 15;4(8):e1000117
references.pmid: 18704157