Human embryonic genome activation initiates at the one-cell stage.
embryonic genome activation (EGA)
fertilization
human one-cell embryo
single-cell RNA-seq
totipotency
transcriptome
zygote
Journal
Cell stem cell
ISSN: 1875-9777
Titre abrégé: Cell Stem Cell
Pays: United States
ID NLM: 101311472
Informations de publication
Date de publication:
03 02 2022
03 02 2022
Historique:
received:
08
04
2021
revised:
24
08
2021
accepted:
29
11
2021
pubmed:
23
12
2021
medline:
19
4
2022
entrez:
22
12
2021
Statut:
ppublish
Résumé
In human embryos, the initiation of transcription (embryonic genome activation [EGA]) occurs by the eight-cell stage, but its exact timing and profile are unclear. To address this, we profiled gene expression at depth in human metaphase II oocytes and bipronuclear (2PN) one-cell embryos. High-resolution single-cell RNA sequencing revealed previously inaccessible oocyte-to-embryo gene expression changes. This confirmed transcript depletion following fertilization (maternal RNA degradation) but also uncovered low-magnitude upregulation of hundreds of spliced transcripts. Gene expression analysis predicted embryonic processes including cell-cycle progression and chromosome maintenance as well as transcriptional activators that included cancer-associated gene regulators. Transcription was disrupted in abnormal monopronuclear (1PN) and tripronuclear (3PN) one-cell embryos. These findings indicate that human embryonic transcription initiates at the one-cell stage, sooner than previously thought. The pattern of gene upregulation promises to illuminate processes involved at the onset of human development, with implications for epigenetic inheritance, stem-cell-derived embryos, and cancer.
Identifiants
pubmed: 34936886
pii: S1934-5909(21)00484-7
doi: 10.1016/j.stem.2021.11.012
pmc: PMC8826644
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
209-216.e4Subventions
Organisme : Medical Research Council
ID : MR/N000080/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S026193/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00014/5
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00014/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12012/5
Pays : United Kingdom
Organisme : Medical Research Council
ID : G1000839
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N020294/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 208363/Z/17/Z
Pays : United Kingdom
Organisme : Cancer Research UK
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/S017593/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/P009506/1
Pays : United Kingdom
Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
Références
Mol Reprod Dev. 2005 Nov;72(3):281-90
pubmed: 16094646
PLoS One. 2013 Sep 10;8(9):e73987
pubmed: 24040138
Protein Cell. 2017 Oct;8(10):776-779
pubmed: 28825190
Nucleic Acids Res. 2015 Apr 20;43(7):e47
pubmed: 25605792
Bioinformatics. 2010 Jan 1;26(1):139-40
pubmed: 19910308
Cell. 2017 Jan 26;168(3):442-459.e20
pubmed: 28111071
Dev Biol. 1988 Jul;128(1):15-20
pubmed: 2454852
Dev Cell. 2019 Jul 1;50(1):5-6
pubmed: 31265812
Brief Bioinform. 2018 Sep 28;19(5):776-792
pubmed: 28334202
Nat Commun. 2020 Oct 1;11(1):4917
pubmed: 33004802
Bioinformatics. 2015 Jan 15;31(2):166-9
pubmed: 25260700
J Reprod Infertil. 2019 Jul-Sep;20(3):127-131
pubmed: 31423415
Nat Rev Mol Cell Biol. 2020 May;21(5):255-267
pubmed: 32071436
Cell. 2018 Jul 12;174(2):391-405.e19
pubmed: 29937225
Nat Commun. 2021 Jun 21;12(1):3804
pubmed: 34155196
J Reprod Fertil. 1997 Mar;109(2):223-8
pubmed: 9155731
Nat Struct Mol Biol. 2013 Sep;20(9):1131-9
pubmed: 23934149
Sci Rep. 2018 Dec 17;8(1):17890
pubmed: 30559372
Biol Reprod. 2006 Dec;75(6):877-84
pubmed: 16943360
Mol Hum Reprod. 2010 Dec;16(12):938-43
pubmed: 20837506
Development. 2016 Oct 1;143(19):3459-3469
pubmed: 27578796
Hum Reprod. 1993 Jul;8(7):1101-9
pubmed: 8408494
Mol Hum Reprod. 1996 May;2(5):299-306
pubmed: 9238696
Dev Cell. 2017 Aug 21;42(4):316-332
pubmed: 28829942
J Biol Chem. 2011 Nov 25;286(47):40743-9
pubmed: 21953461
Reproduction. 2020 Nov;160(5):773-782
pubmed: 33065541
Am J Hum Genet. 2020 Jul 2;107(1):24-33
pubmed: 32502391
Nature. 2013 Aug 29;500(7464):593-7
pubmed: 23892778
Nat Genet. 2016 May;48(5):497-9
pubmed: 26974008
Cell. 2018 Mar 22;173(1):248-259.e15
pubmed: 29526463
Chromosoma. 1988;96(5):341-52
pubmed: 3409776
Biol Reprod. 1987 Sep;37(2):395-401
pubmed: 3676394
Cell. 2020 Jul 9;182(1):127-144.e23
pubmed: 32502394
Nat Methods. 2010 Dec;7(12):1009-15
pubmed: 21057496
Cell. 2016 May 5;165(4):1012-26
pubmed: 27062923
Dev Biol. 1988 Jan;125(1):181-6
pubmed: 3334716
Nat Cell Biol. 2019 Dec;21(12):1468-1478
pubmed: 31792376
Dev Cell. 2005 Sep;9(3):327-38
pubmed: 16139224
EMBO Rep. 2008 Mar;9(3):246-51
pubmed: 18311174
Cell Stem Cell. 2021 Jun 3;28(6):1016-1022.e4
pubmed: 33957081
Bioinformatics. 2014 Feb 15;30(4):523-30
pubmed: 24336805
Nat Genet. 2017 Jun;49(6):941-945
pubmed: 28459456
Cell. 2006 Apr 21;125(2):315-26
pubmed: 16630819
Development. 2000 Sep;127(17):3795-803
pubmed: 10934024
PLoS One. 2013 Oct 15;8(10):e77700
pubmed: 24143257
Nature. 2008 Nov 27;456(7221):470-6
pubmed: 18978772
Trends Genet. 2013 Oct;29(10):569-74
pubmed: 23810203
Dev Biol. 1988 Oct;129(2):304-14
pubmed: 2458285
Gigascience. 2019 Sep 1;8(9):
pubmed: 31531674
Stem Cell Rev Rep. 2009 Jun;5(2):140-58
pubmed: 19521804
Cancer Cell. 2005 May;7(5):433-44
pubmed: 15894264
J Appl Genet. 2018 Feb;59(1):43-57
pubmed: 29344903
J Biol Chem. 2006 Nov 17;281(46):34725-9
pubmed: 16987807
Fertil Steril. 1989 Mar;51(3):460-5
pubmed: 2920845
Nat Biotechnol. 2015 Mar;33(3):290-5
pubmed: 25690850
Nature. 2021 Mar;591(7851):620-626
pubmed: 33731924
Nat Methods. 2018 Apr;15(4):255-261
pubmed: 29481549
Genome Biol. 2010;11(3):R25
pubmed: 20196867
Trends Cell Biol. 2015 Feb;25(2):82-91
pubmed: 25448353
Hum Reprod Update. 2008 Sep-Oct;14(5):431-46
pubmed: 18603645
EMBO J. 2011 May 4;30(9):1841-51
pubmed: 21468028
Cell Rep. 2017 Jul 25;20(4):785-793
pubmed: 28746865
Nat Commun. 2021 Mar 1;12(1):1361
pubmed: 33649327
Nature. 1988 Mar 31;332(6163):459-61
pubmed: 3352746
Science. 2018 Oct 19;362(6412):356-360
pubmed: 30237246
Hum Reprod. 2011 Jun;26(6):1270-83
pubmed: 21502182
Nature. 2021 Mar;591(7851):627-632
pubmed: 33731926
Genome Biol. 2014 Feb 03;15(2):R29
pubmed: 24485249
Reprod Biomed Online. 2004 Oct;9(4):418-24
pubmed: 15511342
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Mol Reprod Dev. 2000 Jun;56(2 Suppl):319-24
pubmed: 10824994
Development. 2011 Sep;138(17):3699-709
pubmed: 21775417
Nat Genet. 2017 Jun;49(6):925-934
pubmed: 28459457
Nature. 2018 May;557(7704):256-260
pubmed: 29720659
Mol Cell Biol. 2012 Jul;32(14):2722-37
pubmed: 22586272
Nat Biotechnol. 2011 Jan;29(1):24-6
pubmed: 21221095
Stem Cells. 2013 Jun;31(6):1051-63
pubmed: 23404835
Protein Cell. 2015 May;6(5):363-372
pubmed: 25894090
J Assist Reprod Genet. 2016 May;33(5):581-588
pubmed: 27052831
Hum Reprod. 2019 May 1;34(5):894-902
pubmed: 30863841
Am J Hum Genet. 2018 Apr 5;102(4):649-657
pubmed: 29606300
Cell Stem Cell. 2019 Nov 7;25(5):697-712.e6
pubmed: 31588047