Donor marker infidelity in transgenic hematopoietic stem cells

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

Research output: Contribution to journalArticle

15 Citations (Scopus)

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 2005

Fingerprint

Hematopoietic Stem Cells
Stem Cells
Myeloid Cells
Transgenes
Transgenic Mice
enhanced green fluorescent protein
B-Lymphocytes
Transplantation
Fluorescence
T-Lymphocytes
Gene Expression
Population

Keywords

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

ASJC Scopus subject areas

  • Cell Biology

Cite this

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

Donor marker infidelity in transgenic hematopoietic stem cells. / Anderson, Daniel A.; Wu, Yanna; Jiang, Shuguang; Zhang, Xingqi; Streeter, Philip; Spangrude, Gerald J.; Archer, David R.; Fleming, William.

In: Stem Cells, Vol. 23, No. 5, 05.2005, p. 638-643.

Research output: Contribution to journalArticle

Anderson, DA, Wu, Y, Jiang, S, Zhang, X, Streeter, P, Spangrude, GJ, Archer, DR & Fleming, W 2005, 'Donor marker infidelity in transgenic hematopoietic stem cells', Stem Cells, vol. 23, no. 5, pp. 638-643. https://doi.org/10.1634/stemcells.2004-0325
Anderson DA, Wu Y, Jiang S, Zhang X, Streeter P, Spangrude GJ et al. Donor marker infidelity in transgenic hematopoietic stem cells. Stem Cells. 2005 May;23(5):638-643. https://doi.org/10.1634/stemcells.2004-0325
Anderson, Daniel A. ; Wu, Yanna ; Jiang, Shuguang ; Zhang, Xingqi ; Streeter, Philip ; Spangrude, Gerald J. ; Archer, David R. ; Fleming, William. / Donor marker infidelity in transgenic hematopoietic stem cells. In: Stem Cells. 2005 ; Vol. 23, No. 5. pp. 638-643.
@article{87599656b42548d6ac805d57014878f9,
title = "Donor marker infidelity in transgenic hematopoietic stem cells",
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.",
keywords = "Bone marrow transplantation, EGFP, Hematopoiesis, Hematopoietic stem cells, Transgenic mouse",
author = "Anderson, {Daniel A.} and Yanna Wu and Shuguang Jiang and Xingqi Zhang and Philip Streeter and Spangrude, {Gerald J.} and Archer, {David R.} and William Fleming",
year = "2005",
month = "5",
doi = "10.1634/stemcells.2004-0325",
language = "English (US)",
volume = "23",
pages = "638--643",
journal = "Stem Cells",
issn = "1066-5099",
publisher = "AlphaMed Press",
number = "5",

}

TY - JOUR

T1 - Donor marker infidelity in transgenic hematopoietic stem cells

AU - Anderson, Daniel A.

AU - Wu, Yanna

AU - Jiang, Shuguang

AU - Zhang, Xingqi

AU - Streeter, Philip

AU - Spangrude, Gerald J.

AU - Archer, David R.

AU - Fleming, William

PY - 2005/5

Y1 - 2005/5

N2 - 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.

AB - 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.

KW - Bone marrow transplantation

KW - EGFP

KW - Hematopoiesis

KW - Hematopoietic stem cells

KW - Transgenic mouse

UR - http://www.scopus.com/inward/record.url?scp=18444405574&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=18444405574&partnerID=8YFLogxK

U2 - 10.1634/stemcells.2004-0325

DO - 10.1634/stemcells.2004-0325

M3 - Article

VL - 23

SP - 638

EP - 643

JO - Stem Cells

JF - Stem Cells

SN - 1066-5099

IS - 5

ER -