Constitutive expression of the ATP-binding cassette transporter ABCG2 enhances the growth potential of early human hematopoietic progenitors

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Farid Ahmed - , Ludwig Maximilian University of Munich, Helmholtz Zentrum München - German Research Center for Environmental Health (Author)
  • Natalia Arseni - , Ludwig Maximilian University of Munich, Helmholtz Zentrum München - German Research Center for Environmental Health (Author)
  • Hanno Glimm - , German Cancer Research Center, partner site Dresden, National Center for Tumor Diseases Dresden, National Center for Tumor Diseases (NCT) Heidelberg (Author)
  • Wolfgang Hiddemann - , Ludwig Maximilian University of Munich, Helmholtz Zentrum München - German Research Center for Environmental Health (Author)
  • Christian Buske - , Ludwig Maximilian University of Munich, Helmholtz Zentrum München - German Research Center for Environmental Health (Author)
  • Michaela Feuring-Buske - , Ludwig Maximilian University of Munich, Helmholtz Zentrum München - German Research Center for Environmental Health (Author)

Abstract

The ATP-binding cassette transporter, ABCG2, is a molecular determinant of the side population phenotype, which is enriched for stem and progenitor cells in various nonhematopoietic and hematopoietic tissues. ABCG2 is highly expressed in hematopoietic progenitors and silenced in differentiated hematopoietic cells, suggesting a role of ABCG2 in early hematopoiesis. To test whether ABCG2 is involved in human hematopoietic development, we retrovirally transduced umbilical cord blood-derived early hematopoietic cells and analyzed hematopoiesis in vitro and in vivo. ABCG2 increased the number of clonogenic progenitors in vitro, including the most primitive colony-forming unit-granulocyte, erythroid, macrophage, megakaryocyte, by twofold (n = 14; p < .0005). Furthermore, ABCG2 induced a threefold increase in the replating capacity of primary colonies (n = 9; p < .01). In addition, ABCG2 impaired the development of CD19+ lymphoid cells in vitro. In transplanted NOD/SCID mice, the ATP-binding cassette transporter decreased the number of human B-lymphoid cells, resulting in an inversion of the lymphoid/myeloid ratio. ABCG2 enhanced the proportion of CD34+ progenitor cells in vivo (n = 4; p < .05) and enhanced the most primitive human progenitor pool, as determined by limiting dilution competitive repopulating unit assay (p < .034). Our data characterize ABCG2 as a regulatory protein of early human hematopoietic development.

Details

Original languageEnglish
Pages (from-to)810-818
Number of pages9
JournalStem cells
Volume26
Issue number3
Publication statusPublished - Mar 2008
Peer-reviewedYes

External IDs

PubMed 18055445

Keywords

Sustainable Development Goals

ASJC Scopus subject areas

Keywords

  • ABCG2, Hematopoiesis, Human progenitor cells