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PMID: 27062923 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Single-Cell RNA-Seq Reveals Lineage and X Chromosome Dynamics in Human Preimplantation Embryos.

Cell ·Vol. 165 ·No. 4 ·2016-05-05 ·Pages 1012-26

Petropoulos S, Edsgärd D, Reinius B, Deng Q, Panula SP, Codeluppi S, Plaza Reyes A, Linnarsson S, Sandberg R, Lanner F

Abstract

Mouse studies have been instrumental in forming our current understanding of early cell-lineage decisions; however, similar insights into the early human development are severely limited. Here, we present a comprehensive transcriptional map of human embryo development, including the sequenced transcriptomes of 1,529 individual cells from 88 human preimplantation embryos. These data show that cells undergo an intermediate state of co-expression of lineage-specific genes, followed by a concurrent establishment of the trophectoderm, epiblast, and primitive endoderm lineages, which coincide with blastocyst formation. Female cells of all three lineages achieve dosage compensation of X chromosome RNA levels prior to implantation. However, in contrast to the mouse, XIST is transcribed from both alleles throughout the progression of this expression dampening, and X chromosome genes maintain biallelic expression while dosage compensation proceeds. We envision broad utility of this transcriptional atlas in future studies on human development as well as in stem cell research.

MeSH Terms
Blastocyst/metabolism Blastocyst Inner Cell Mass/metabolism Chromosomes, Human, X Dosage Compensation, Genetic Female Humans Male RNA, Long Noncoding/genetics Sequence Analysis, RNA Sex Characteristics Single-Cell Analysis Transcriptome
Chemicals
RNA, Long Noncoding XIST non-coding RNA
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Petropoulos Sophie
Department of Clinical Science, Intervention and Technology, Karolinska Institutet, and Division of Obstetrics and Gynecology, Karolinska Universitetssjukhuset, 141 86 Stockholm, Sweden; Ludwig Institute for Cancer Research, Box 240, 171 77 Stockholm, Sweden.
Edsgärd Daniel
Ludwig Institute for Cancer Research, Box 240, 171 77 Stockholm, Sweden; Department of Cell and Molecular Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.
Reinius Björn
Ludwig Institute for Cancer Research, Box 240, 171 77 Stockholm, Sweden; Department of Cell and Molecular Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.
Deng Qiaolin
Ludwig Institute for Cancer Research, Box 240, 171 77 Stockholm, Sweden; Department of Cell and Molecular Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.
Panula Sarita Pauliina
Department of Clinical Science, Intervention and Technology, Karolinska Institutet, and Division of Obstetrics and Gynecology, Karolinska Universitetssjukhuset, 141 86 Stockholm, Sweden.
Codeluppi Simone
Department of Physiology and Pharmacology, Karolinska Institutet, 171 77 Stockholm, Sweden; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77 Stockholm, Sweden.
Plaza Reyes Alvaro
Department of Clinical Science, Intervention and Technology, Karolinska Institutet, and Division of Obstetrics and Gynecology, Karolinska Universitetssjukhuset, 141 86 Stockholm, Sweden.
Linnarsson Sten
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77 Stockholm, Sweden.
Sandberg Rickard
Ludwig Institute for Cancer Research, Box 240, 171 77 Stockholm, Sweden; Department of Cell and Molecular Biology, Karolinska Institutet, 171 77 Stockholm, Sweden. Electronic address: rickard.sandberg@ki.se.
Lanner Fredrik
Department of Clinical Science, Intervention and Technology, Karolinska Institutet, and Division of Obstetrics and Gynecology, Karolinska Universitetssjukhuset, 141 86 Stockholm, Sweden. Electronic address: fredrik.lanner@ki.se.
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2016.03.023
Email
rickard.sandberg@ki.se
fredrik.lanner@ki.se
Published
2016-05-05
Epub
2016-00-07
Pages
1012-26
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC4868821
Subset
IM
Grants
European Research Council · 648842 · International
Corrections
CommentIn
PMID: 27153491
ErratumIn
PMID: 27662094
CommentIn
PMID: 27919070
CommentIn
PMID: 30037898
External Links
PubMed source DOI: 10.1016/j.cell.2016.03.023 PMC Full Text View journal details
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