title: Multipotent hematopoietic progenitors divide asymmetrically to create progenitors of the lymphomyeloid and erythromyeloid lineages.
abstract: Hematopoietic stem and progenitor cells (HSPCs) can self-renew and create committed progenitors, a process supposed to involve asymmetric cell divisions (ACDs). Previously, we had linked the kinetics of CD133 expression with ACDs but failed to detect asymmetric segregation of classical CD133 epitopes on fixed, mitotic HSPCs. Now, by using a novel anti-CD133 antibody (HC7), we confirmed the occurrence of asymmetric CD133 segregation on paraformaldehyde-fixed and living HSPCs. After showing that HC7 binding does not recognizably affect biological features of human HSPCs, we studied ACDs in different HSPC subtypes and determined the developmental potential of arising daughter cells at the single-cell level. Approximately 70% of the HSPCs of the multipotent progenitor (MPP) fraction studied performed ACDs, and about 25% generated lymphoid-primed multipotent progenitor (LMPP) as wells as erythromyeloid progenitor (EMP) daughter cells. Since MPPs hardly created daughter cells maintaining MPP characteristics, our data suggest that under conventional culture conditions, ACDs are lineage instructive rather than self-renewing.
authors.affiliation: Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Virchowstraße 179, 45147 Essen, Germany; German Cancer Consortium (DKTK). Electronic address: andre.goergens@uk-essen.de.
authors.forename: André
authors.initials: A
authors.lastname: Görgens
authors.affiliation: Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Virchowstraße 179, 45147 Essen, Germany.
authors.forename: Anna-Kristin
authors.initials: AK
authors.lastname: Ludwig
authors.affiliation: Department of Hematology, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, 45122 Essen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Möllmann
authors.affiliation: Institute of Virology, University Hospital Essen, University of Duisburg-Essen, Virchowstraße 179, 45147 Essen, Germany.
authors.forename: Adalbert
authors.initials: A
authors.lastname: Krawczyk
authors.affiliation: Department of Hematology, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, 45122 Essen, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Dürig
authors.affiliation: Riley Hospital for Children, Indiana University School of Medicine, 705 Riley Hospital Drive, Indianapolis, IN 46202, USA.
authors.forename: Helmut
authors.initials: H
authors.lastname: Hanenberg
authors.affiliation: Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Virchowstraße 179, 45147 Essen, Germany; German Cancer Consortium (DKTK).
authors.forename: Peter A
authors.initials: PA
authors.lastname: Horn
authors.affiliation: Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Virchowstraße 179, 45147 Essen, Germany; German Cancer Consortium (DKTK). Electronic address: bernd.giebel@uk-essen.de.
authors.forename: Bernd
authors.initials: B
authors.lastname: Giebel
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D060049:Asymmetric Cell Division; D002448:Cell Adhesion; D002454:Cell Differentiation; D019070:Cell Lineage; D002465:Cell Movement; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000378:metabolism; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D064593:Heterografts; D006801:Humans; D016130:Immunophenotyping; D054503:Lymphoid Progenitor Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D023461:Myeloid Progenitor Cells / Q000166:cytology* / Q000378:metabolism; D010641:Phenotype
chemical_list: D000954:Antigens, Surface