Integrated pseudotime analysis of human pre-implantation embryo single-cell transcriptomes reveals the dynamics of lineage specification

被引：147

作者：

Meistermann, Dimitri ^{[1
,3
]}

Bruneau, Alexandre ^{[1
]}

Loubersac, Sophie ^{[1
,2
]}

Reignier, Arnaud ^{[1
,2
]}

Firmin, Julie ^{[1
,2
]}

Francois-Campion, Valentin ^{[1
]}

Kilens, Stephanie ^{[1
]}

Lelievre, Yohann ^{[3
]}

Lammers, Jenna ^{[2
]}

Feyeux, Magalie ^{[1
,4
]}

Hulin, Phillipe ^{[4
]}

Nedellec, Steven ^{[4
]}

Bretin, Betty ^{[1
]}

Castel, Gael ^{[1
]}

Allegre, Nicolas ^{[9
]}

Covin, Simon ^{[1
]}

Bihouee, Audrey ^{[4
,5
]}

Soumillon, Magali ^{[6
,7
,8
,11
]}

Mikkelsen, Tarjei ^{[6
,7
,8
,12
]}

Barriere, Paul ^{[1
,2
]}

Chazaud, Claire ^{[9
]}

Chappell, Joel ^{[10
]}

Pasque, Vincent ^{[10
]}

Bourdon, Jeremie ^{[3
]}

Freour, Thomas ^{[1
,2
]}

David, Laurent ^{[1
,4
]}

机构：

[1] Univ Nantes, CHU Nantes, Ctr Rech Transplantat & Immunol, INSERM,UMR 1064,ITUN, F-44000 Nantes, France

[2] Univ Nantes, Serv Biol Reprod, CHU Nantes, F-44000 Nantes, France

[3] Univ Nantes, CNRS, LS2N, Nantes, France

[4] Univ Nantes, CHU Nantes, UMS 3556, INSERM,CNRS,SFR Sante,FED 4203,INSERM UMS 016, Nantes, France

[5] Univ Nantes, CNRS, INSERM, Inst Thorax, Nantes, France

[6] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA

[7] Broad Inst, Cambridge, MA 02142 USA

[8] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA

[9] Univ Clermont Auvergne, Fac Med, GReD Lab, CNRS,INSERM,CRBC, F-63000 Clermont Ferrand, France

[10] Univ Leuven, Inst Single Cell Omics, Dept Dev & Regenerat, KU Leuven,Leuven Stem Cell Inst, Herestr 49, B-3000 Leuven, Belgium

[11] Flexomics LLC, 38 Wareham St,Fl 3, Boston, MA 02118 USA

[12] 10x Genom, 7068 Koll Ctr Pkwy 401, Pleasanton, CA 94566 USA

来源：

CELL STEM CELL | 2021年 / 28卷 / 09期

关键词：

COLONY-STIMULATING FACTOR; TROPHECTODERM MORPHOLOGY; PRIMITIVE ENDODERM; PREDICTS OUTCOMES; SELF-ORGANIZATION; HUMAN BLASTOCYST; LIVE BIRTH; MOUSE; NAIVE; IMPLANTATION;

D O I：

10.1016/j.stem.2021.04.027

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Understanding lineage specification during human pre-implantation development is a gateway to improving assisted reproductive technologies and stem cell research. Here we employ pseudotime analysis of single-cell RNA sequencing (scRNA-seq) data to reconstruct early mouse and human embryo development. Using time- lapse imaging of annotated embryos, we provide an integrated, ordered, and continuous analysis of transcriptomics changes throughout human development. We reveal that human trophectoderm/inner cell mass transcriptomes diverge at the transition from the B2 to the B3 blastocyst stage, just before blastocyst expansion. We explore the dynamics of the fate markers IFI16 and GATA4 and show that they gradually become mutually exclusive upon establishment of epiblast and primitive endoderm fates, respectively. We also provide evidence that NR2F2 marks trophectoderm maturation, initiating from the polar side, and subsequently spreads to all cells after implantation. Our study pinpoints the precise timing of lineage specification events in the human embryo and identifies transcriptomics hallmarks and cell fate markers.

引用

页码：1625 / +

页数：22

共 88 条

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