title: Heterogeneity of Mesp1+ mesoderm revealed by single-cell RNA-seq.
abstract: Mesp1 is a transcription factor that promotes differentiation of pluripotent cells into different mesoderm lineages including hematopoietic, cardiac and skeletal myogenic. This occurs via at least two transient cell populations: a common hematopoietic/cardiac progenitor population and a common cardiac/skeletal myogenic progenitor population. It is not established whether Mesp1-induced mesoderm cells are intrinsically heterogeneous, or are simply capable of multiple lineage decisions. In the current study, we applied single-cell RNA-seq to analyze Mesp1+ mesoderm. Initial whole transcriptome analysis showed a surprising homogeneity among Mesp1-induced mesoderm cells. However, this apparent global homogeneity masked an intrinsic heterogeneity revealed by interrogating a panel of early mesoderm patterning factors. This approach enabled discovery of subpopulations primed for hematopoietic or cardiac development. These studies demonstrate the heterogeneic nature of Mesp1+ mesoderm.
authors.affiliation: Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA; Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: sschan@umn.edu.
authors.forename: Sunny Sun-Kin
authors.initials: SS
authors.lastname: Chan
authors.affiliation: Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: hw.chan@hotmail.com.
authors.forename: Howe H W
authors.initials: HHW
authors.lastname: Chan
authors.affiliation: Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA; Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: kyba@umn.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Kyba
mesh_terms: D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D006410:Hematopoiesis / Q000502:physiology; D008648:Mesoderm / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D032342:Muscle Cells / Q000166:cytology* / Q000502:physiology; D012313:RNA / Q000235:genetics; D017423:Sequence Analysis, RNA / Q000379:methods; D014018:Tissue Distribution
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D012313:RNA; C101538:Mesp1 protein, mouse
keywords: Cardiac development; Hematopoiesis; Mesoderm patterning; Mesp1; Single-cell RNA-seq