title: Distinct myeloid progenitor-differentiation pathways identified through single-cell RNA sequencing.
abstract: According to current models of hematopoiesis, lymphoid-primed multi-potent progenitors (LMPPs) (Lin(-)Sca-1(+)c-Kit(+)CD34(+)Flt3(hi)) and common myeloid progenitors (CMPs) (Lin(-)Sca-1(+)c-Kit(+)CD34(+)CD41(hi)) establish an early branch point for separate lineage-commitment pathways from hematopoietic stem cells, with the notable exception that both pathways are proposed to generate all myeloid innate immune cell types through the same myeloid-restricted pre-granulocyte-macrophage progenitor (pre-GM) (Lin(-)Sca-1(-)c-Kit(+)CD41(-)FcγRII/III(-)CD150(-)CD105(-)). By single-cell transcriptome profiling of pre-GMs, we identified distinct myeloid differentiation pathways: a pathway expressing the gene encoding the transcription factor GATA-1 generated mast cells, eosinophils, megakaryocytes and erythroid cells, and a pathway lacking expression of that gene generated monocytes, neutrophils and lymphocytes. These results identify an early hematopoietic-lineage bifurcation that separates the myeloid lineages before their segregation from other hematopoietic-lineage potential.
authors.affiliation: MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.|Institute for Stem Cell Research, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Roy
authors.initials: R
authors.lastname: Drissen
authors.affiliation: Institute for Stem Cell Research, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Natalija
authors.initials: N
authors.lastname: Buza-Vidas
authors.affiliation: MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.|Haematopoietic Stem Cell Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Petter
authors.initials: P
authors.lastname: Woll
authors.affiliation: MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Supat
authors.initials: S
authors.lastname: Thongjuea
authors.affiliation: MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.|Institute for Stem Cell Research, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Adriana
authors.initials: A
authors.lastname: Gambardella
authors.affiliation: MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.|Haematopoietic Stem Cell Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Alice
authors.initials: A
authors.lastname: Giustacchini
authors.affiliation: EMBL Mouse Biology Program, Monterotondo, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Mancini
authors.affiliation: Division of Molecular Hematology, University of Lund, Sweden.
authors.forename: Alya
authors.initials: A
authors.lastname: Zriwil
authors.affiliation: MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.|Haematopoietic Stem Cell Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Lutteropp
authors.affiliation: MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.|Institute for Stem Cell Research, University of Edinburgh, Edinburgh, United Kingdom.|EMBL Mouse Biology Program, Monterotondo, Italy.
authors.forename: Amit
authors.initials: A
authors.lastname: Grover
authors.affiliation: MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.|Haematopoietic Stem Cell Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Adam
authors.initials: A
authors.lastname: Mead
authors.affiliation: Division of Molecular Hematology, University of Lund, Sweden.
authors.forename: Ewa
authors.initials: E
authors.lastname: Sitnicka
authors.affiliation: MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.|Haematopoietic Stem Cell Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Sten Eirik W
authors.initials: SEW
authors.lastname: Jacobsen
authors.affiliation: MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.|Institute for Stem Cell Research, University of Edinburgh, Edinburgh, United Kingdom.|EMBL Mouse Biology Program, Monterotondo, Italy.
authors.forename: Claus
authors.initials: C
authors.lastname: Nerlov
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D019295:Computational Biology; D050982:GATA1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D006410:Hematopoiesis; D007113:Immunity, Innate; D008214:Lymphocytes / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000502:physiology*; D023461:Myeloid Progenitor Cells / Q000502:physiology*; D017423:Sequence Analysis, RNA; D059010:Single-Cell Analysis; D046888:Tissue Array Analysis; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3