title: Serum-Based Culture Conditions Provoke Gene Expression Variability in Mouse Embryonic Stem Cells as Revealed by Single-Cell Analysis.
abstract: Variation in gene expression is an important feature of mouse embryonic stem cells (ESCs). However, the mechanisms responsible for global gene expression variation in ESCs are not fully understood. We performed single-cell mRNA-seq analysis of mouse ESCs and uncovered significant heterogeneity in ESCs cultured in serum. We define highly variable gene clusters with distinct chromatin states and show that bivalent genes are prone to expression variation. At the same time, we identify an ESC-priming pathway that initiates the exit from the naive ESC state. Finally, we provide evidence that a large proportion of intracellular network variability is due to the extracellular culture environment. Serum-free culture reduces cellular heterogeneity and transcriptome variation in ESCs.
authors.affiliation: Division of Pediatric Hematology/Oncology, Dana Farber Cancer Institute and Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA; Center for Stem Cell and Regenerative Medicine, Zhejiang University School of Medicine, Hangzhou 310058, China. Electronic address: ggj@zju.edu.cn.
authors.forename: Guoji
authors.initials: G
authors.lastname: Guo
authors.affiliation: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard TH Chan School of Public Health, Boston, MA 02115, USA.
authors.forename: Luca
authors.initials: L
authors.lastname: Pinello
authors.affiliation: Division of Pediatric Hematology/Oncology, Dana Farber Cancer Institute and Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA; Center for Stem Cell and Regenerative Medicine, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Han
authors.affiliation: Center for Stem Cell and Regenerative Medicine, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Shujing
authors.initials: S
authors.lastname: Lai
authors.affiliation: Life Sciences Institute, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Li
authors.initials: L
authors.lastname: Shen
authors.affiliation: Molecular Genetics Core Facility, Boston Children's Hospital, Boston, MA 02115, USA.
authors.forename: Ta-Wei
authors.initials: TW
authors.lastname: Lin
authors.affiliation: Boston Open Labs, Cambridge, MA 02138, USA.
authors.forename: Keyong
authors.initials: K
authors.lastname: Zou
authors.affiliation: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard TH Chan School of Public Health, Boston, MA 02115, USA. Electronic address: gcyuan@jimmy.harvard.edu.
authors.forename: Guo-Cheng
authors.initials: GC
authors.lastname: Yuan
authors.affiliation: Division of Pediatric Hematology/Oncology, Dana Farber Cancer Institute and Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute, Boston, MA 02115, USA. Electronic address: stuart_orkin@dfci.harvard.edu.
authors.forename: Stuart H
authors.initials: SH
authors.lastname: Orkin
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods; D002460:Cell Line; D042002:Chromatin Assembly and Disassembly; D003470:Culture Media / Q000737:chemistry; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D044967:Serum; D059010:Single-Cell Analysis / Q000379:methods*; D059467:Transcriptome
chemical_list: D003470:Culture Media