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Cell. 2016 May 5;165(4):1012-26. doi: 10.1016/j.cell.2016.03.023. Epub 2016 Apr 7.

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

Author information

1
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.
2
Ludwig Institute for Cancer Research, Box 240, 171 77 Stockholm, Sweden; Department of Cell and Molecular Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.
3
Department of Clinical Science, Intervention and Technology, Karolinska Institutet, and Division of Obstetrics and Gynecology, Karolinska Universitetssjukhuset, 141 86 Stockholm, Sweden.
4
Department of Physiology and Pharmacology, Karolinska Institutet, 171 77 Stockholm, Sweden; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77 Stockholm, Sweden.
5
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77 Stockholm, Sweden.
6
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.
7
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.

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.

PMID:
27062923
PMCID:
PMC4868821
DOI:
10.1016/j.cell.2016.03.023
[Indexed for MEDLINE]
Free PMC Article

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