title: An atlas of transcriptional, chromatin accessibility, and surface marker changes in human mesoderm development.
abstract: Mesoderm is the developmental precursor to myriad human tissues including bone, heart, and skeletal muscle. Unravelling the molecular events through which these lineages become diversified from one another is integral to developmental biology and understanding changes in cellular fate. To this end, we developed an in vitro system to differentiate human pluripotent stem cells through primitive streak intermediates into paraxial mesoderm and its derivatives (somites, sclerotome, dermomyotome) and separately, into lateral mesoderm and its derivatives (cardiac mesoderm). Whole-population and single-cell analyses of these purified populations of human mesoderm lineages through RNA-seq, ATAC-seq, and high-throughput surface marker screens illustrated how transcriptional changes co-occur with changes in open chromatin and surface marker landscapes throughout human mesoderm development. This molecular atlas will facilitate study of human mesoderm development (which cannot be interrogated in vivo due to restrictions on human embryo studies) and provides a broad resource for the study of gene regulation in development at the single-cell level, knowledge that might one day be exploited for regenerative medicine.
authors.affiliation: Department of Genetics and Department of Computer Science, Stanford University, Stanford, California 94305, USA.
authors.forename: Pang Wei
authors.initials: PW
authors.lastname: Koh
authors.affiliation: Department of Developmental Biology, Institute for Stem Cell Biology and Regenerative Medicine, Ludwig Center for Cancer Stem Cell Biology and Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Rahul
authors.initials: R
authors.lastname: Sinha
authors.affiliation: Department of Developmental Biology, Institute for Stem Cell Biology and Regenerative Medicine, Ludwig Center for Cancer Stem Cell Biology and Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Amira A
authors.initials: AA
authors.lastname: Barkal
authors.affiliation: Department of Developmental Biology, Institute for Stem Cell Biology and Regenerative Medicine, Ludwig Center for Cancer Stem Cell Biology and Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Morganti
authors.affiliation: Department of Developmental Biology, Institute for Stem Cell Biology and Regenerative Medicine, Ludwig Center for Cancer Stem Cell Biology and Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Chen
authors.affiliation: Department of Developmental Biology, Institute for Stem Cell Biology and Regenerative Medicine, Ludwig Center for Cancer Stem Cell Biology and Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Irving L
authors.initials: IL
authors.lastname: Weissman
authors.affiliation: Stem Cell &Regenerative Biology Group, Genome Institute of Singapore, A*STAR, Singapore 138672, Singapore.
authors.forename: Lay Teng
authors.initials: LT
authors.lastname: Ang
authors.affiliation: Department of Genetics and Department of Computer Science, Stanford University, Stanford, California 94305, USA.
authors.forename: Anshul
authors.initials: A
authors.lastname: Kundaje
authors.affiliation: Department of Developmental Biology, Institute for Stem Cell Biology and Regenerative Medicine, Ludwig Center for Cancer Stem Cell Biology and Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Kyle M
authors.initials: KM
authors.lastname: Loh
mesh_terms: D015415:Biomarkers; D002454:Cell Differentiation; D002843:Chromatin; D006801:Humans; D008648:Mesoderm / Q000166:cytology / Q000196:embryology / Q000502:physiology*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000502:physiology; D014158:Transcription, Genetic
chemical_list: D015415:Biomarkers; D002843:Chromatin