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Tissue-Specific Stem Cells
Version of Record online: 20 AUG 2012
Copyright © 2012 AlphaMed Press
Volume 30, Issue 9, pages 1961–1970, September 2012
How to Cite
Zavidij, O., Ball, C. R., Herbst, F., Oppel, F., Fessler, S., Schmidt, M., von Kalle, C. and Glimm, H. (2012), Stable Long-Term Blood Formation by Stem Cells in Murine Steady-State Hematopoiesis. STEM CELLS, 30: 1961–1970. doi: 10.1002/stem.1151
Author contributions: O.Z. and C.R.B.: conception and design, collection and assembly of data, data analysis and interpretation, and manuscript writing; F.H.: data analysis and interpretation; F.O. and S.F.: collection of data; M.S.: conception and design and data analysis and interpretation; C.K.: conception and design and manuscript writing; H.G.: conception and design, data analysis and interpretation, and manuscript writing. O.Z. and C.R.B. contributed equally to this article.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS June 13, 2012.
- Issue online: 20 AUG 2012
- Version of Record online: 20 AUG 2012
- Accepted manuscript online: 13 JUN 2012 02:46PM EST
- Manuscript Accepted: 19 MAY 2012
- Manuscript Received: 30 JAN 2012
- German Cancer Aid (Deutsche Krebshilfe. Grant Number: 107217
- German Research Foundation. Grant Numbers: DFG, SFB 873
- Hematopoietic stem cells;
- In vivo marking;
- Lentiviral vector;
- Adult stem cells;
- Steady-state hematopoiesis
Hematopoietic stem cells (HSCs) generate all mature blood cells during the whole lifespan of an individual. However, the clonal contribution of individual HSC and progenitor cells in steady-state hematopoiesis is poorly understood. To investigate the activity of HSCs under steady-state conditions, murine HSC and progenitor cells were genetically marked in vivo by integrating lentiviral vectors (LVs) encoding green fluorescent protein (GFP). Hematopoietic contribution of individual marked clones was monitored by determination of lentiviral integration sites using highly sensitive linear amplification-mediated-polymerase chain reaction. A remarkably stable small proportion of hematopoietic cells expressed GFP in LV-injected animals for up to 24 months, indicating stable marking of murine steady-state hematopoiesis. Analysis of the lentiviral integration sites revealed that multiple hematopoietic clones with both myeloid and lymphoid differentiation potential contributed to long-term hematopoiesis. In contrast to intrafemoral vector injection, intravenous administration of LV preferentially targeted short-lived progenitor cells. Myelosuppressive treatment of mice prior to LV-injection did not affect the marking efficiency. Our study represents the first continuous analysis of clonal behavior of genetically marked hematopoietic cells in an unmanipulated system, providing evidence that multiple clones are simultaneously active in murine steady-state hematopoiesis. Stem Cells2012;30:1961–1970