title: Macrophage colony-stimulating factor receptor marks and regulates a fetal myeloid-primed B-cell progenitor in mice.
abstract: Although it is well established that unique B-cell lineages develop through distinct regulatory mechanisms during embryonic development, much less is understood about the differences between embryonic and adult B-cell progenitor cells, likely to underpin the genetics and biology of infant and childhood PreB acute lymphoblastic leukemia (PreB-ALL), initiated by distinct leukemia-initiating translocations during embryonic development. Herein, we establish that a distinct subset of the earliest CD19(+) B-cell progenitors emerging in the E13.5 mouse fetal liver express the colony-stimulating factor-1 receptor (CSF1R), previously thought to be expressed, and play a lineage-restricted role in development of myeloid lineages, and macrophages in particular. These early embryonic CSF1R(+)CD19(+) ProB cells also express multiple other myeloid genes and, in line with this, possess residual myeloid as well as B-cell, but not T-cell lineage potential. Notably, these CSF1R(+) myeloid-primed ProB cells are uniquely present in a narrow window of embryonic fetal liver hematopoiesis and do not persist in adult bone marrow. Moreover, analysis of CSF1R-deficient mice establishes a distinct role of CSF1R in fetal B-lymphopoiesis. CSF1R(+) myeloid-primed embryonic ProB cells are relevant for infant and childhood PreB-ALLs, which frequently have a bi-phenotypic B-myeloid phenotype, and in which CSF1R-rearrangements have recently been reported.
authors.affiliation: Lund Research Center for Stem Cell Biology and Cell Therapy, Division of Molecular Hematology, Department of Laboratory Medicine.
authors.forename: Alya
authors.initials: A
authors.lastname: Zriwil
authors.affiliation: Division of Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, Lund, Sweden;
authors.forename: Charlotta
authors.initials: C
authors.lastname: Böiers
authors.affiliation: Lund Research Center for Stem Cell Biology and Cell Therapy, Division of Molecular Hematology, Department of Laboratory Medicine.
authors.forename: Lilian
authors.initials: L
authors.lastname: Wittmann
authors.affiliation: Haematopoietic Stem Cell Biology Laboratory, MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom; and.
authors.forename: Joanna C A
authors.initials: JC
authors.lastname: Green
authors.affiliation: Wallenberg Institute for Regenerative Medicine, Department of Cell and Molecular Biology and Department of Medicine Huddinge, Karolinska Institutet and Center for Hematology and Regenerative Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Petter S
authors.initials: PS
authors.lastname: Woll
authors.affiliation: Haematopoietic Stem Cell Biology Laboratory, MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom; and Wallenberg Institute for Regenerative Medicine, Department of Cell and Molecular Biology and Department of Medicine Huddinge, Karolinska Institutet and Center for Hematology and Regenerative Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Sten Eirik W
authors.initials: SE
authors.lastname: Jacobsen
authors.affiliation: Lund Research Center for Stem Cell Biology and Cell Therapy, Division of Molecular Hematology, Department of Laboratory Medicine.
authors.forename: Ewa
authors.initials: E
authors.lastname: Sitnicka
mesh_terms: D000818:Animals; D019070:Cell Lineage / Q000502:physiology*; D005333:Fetus / Q000166:cytology / Q000378:metabolism*; D038041:Lymphopoiesis / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology / Q000378:metabolism*; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: C000604004:Csf1r protein, mouse; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor