Donor marker infidelity in transgenic hematopoietic stem cells

Daniel A. Anderson, Yanna Wu, Shuguang Jiang, Xingqi Zhang, Philip R. Streeter, Gerald J. Spangrude, David R. Archer, William H. Fleming

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Transgenic marking approaches are increasingly used to evaluate the developmental potential of stem cells. However, cell fate mapping studies using different transgenic marking systems have produced conflicting results. These disparate findings may be due in part to the infidelity of donor marker gene expression. Analysis of hematopoietic stem cells (c-Kit+, Sca-1 +, lineage marker- [KSL]) from a transgenic mouse (1Osb) engineered to ubiquitously express the enhanced green fluorescent protein (EGFP) reveals two distinct populations. Forty percent of KSL cells demonstrate intermediate levels of EGFP fluorescence and differentiate into subpopulations of B cells, T cells, and myeloid cells that do not express EGFP. By contrast, progeny of the remaining 60% of KSL cells are almost exclusively EGFP bright. Long-term multilineage hematopoietic reconstitution and serial transplantation experiments show that these differences in EGFP are a property of self-renewing stem cells. Furthermore, both the transgene integration site and the activation status of a cell are important determinants of EGFP expression. These results indicate that a combination of donor cell markers is required to reliably track the full differentiation potential of transgenic stem cells.

Original languageEnglish (US)
Pages (from-to)638-643
Number of pages6
JournalStem Cells
Volume23
Issue number5
DOIs
StatePublished - May 1 2005

Keywords

  • Bone marrow transplantation
  • EGFP
  • Hematopoiesis
  • Hematopoietic stem cells
  • Transgenic mouse

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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  • Cite this

    Anderson, D. A., Wu, Y., Jiang, S., Zhang, X., Streeter, P. R., Spangrude, G. J., Archer, D. R., & Fleming, W. H. (2005). Donor marker infidelity in transgenic hematopoietic stem cells. Stem Cells, 23(5), 638-643. https://doi.org/10.1634/stemcells.2004-0325