title: Single-Cell RNA-Seq Reveals Lineage and X Chromosome Dynamics in Human Preimplantation Embryos.
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.
authors.affiliation: 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.
authors.forename: Sophie
authors.initials: S
authors.lastname: Petropoulos
authors.affiliation: Ludwig Institute for Cancer Research, Box 240, 171 77 Stockholm, Sweden; Department of Cell and Molecular Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Edsgärd
authors.affiliation: Ludwig Institute for Cancer Research, Box 240, 171 77 Stockholm, Sweden; Department of Cell and Molecular Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Reinius
authors.affiliation: Ludwig Institute for Cancer Research, Box 240, 171 77 Stockholm, Sweden; Department of Cell and Molecular Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.
authors.forename: Qiaolin
authors.initials: Q
authors.lastname: Deng
authors.affiliation: Department of Clinical Science, Intervention and Technology, Karolinska Institutet, and Division of Obstetrics and Gynecology, Karolinska Universitetssjukhuset, 141 86 Stockholm, Sweden.
authors.forename: Sarita Pauliina
authors.initials: SP
authors.lastname: Panula
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, 171 77 Stockholm, Sweden; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77 Stockholm, Sweden.
authors.forename: Simone
authors.initials: S
authors.lastname: Codeluppi
authors.affiliation: Department of Clinical Science, Intervention and Technology, Karolinska Institutet, and Division of Obstetrics and Gynecology, Karolinska Universitetssjukhuset, 141 86 Stockholm, Sweden.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Plaza Reyes
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77 Stockholm, Sweden.
authors.forename: Sten
authors.initials: S
authors.lastname: Linnarsson
authors.affiliation: 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.
authors.forename: Rickard
authors.initials: R
authors.lastname: Sandberg
authors.affiliation: 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.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Lanner
mesh_terms: D001755:Blastocyst / Q000378:metabolism*; D053624:Blastocyst Inner Cell Mass / Q000378:metabolism; D041321:Chromosomes, Human, X; D004303:Dosage Compensation, Genetic; D005260:Female; D006801:Humans; D008297:Male; D062085:RNA, Long Noncoding / Q000235:genetics; D017423:Sequence Analysis, RNA; D012727:Sex Characteristics; D059010:Single-Cell Analysis; D059467:Transcriptome
chemical_list: D062085:RNA, Long Noncoding; C077885:XIST non-coding RNA