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Stem Cell Reports. 2014 Dec 9;3(6):1058-72. doi: 10.1016/j.stemcr.2014.09.016. Epub 2014 Oct 23.

Multipotent hematopoietic progenitors divide asymmetrically to create progenitors of the lymphomyeloid and erythromyeloid lineages.

Author information

1
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.
2
Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Virchowstraße 179, 45147 Essen, Germany.
3
Department of Hematology, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, 45122 Essen, Germany.
4
Institute of Virology, University Hospital Essen, University of Duisburg-Essen, Virchowstraße 179, 45147 Essen, Germany.
5
Riley Hospital for Children, Indiana University School of Medicine, 705 Riley Hospital Drive, Indianapolis, IN 46202, USA.
6
Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Virchowstraße 179, 45147 Essen, Germany; German Cancer Consortium (DKTK).
7
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.

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.

PMID:
25448068
PMCID:
PMC4263999
DOI:
10.1016/j.stemcr.2014.09.016
[Indexed for MEDLINE]
Free PMC Article

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