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A novel assay to trace proliferation history in vivo reveals that enhanced divisional kinetics accompany loss of hematopoietic stem cell self-renewal
Lund University, Lund, Sweden.ORCID iD: 0000-0002-3576-2393
Lund University, Department of Experimental Medical Science, Sweden.
2008 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 3, no 11, art. no. e3710- p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The maintenance of lifelong blood cell production ultimately rests on rare hematopoietic stem cells (HSCs) that reside in the bone marrow microenvironment. HSCs are traditionally viewed as mitotically quiescent relative to their committed progeny. However, traditional techniques for assessing proliferation activity in vivo, such as measurement of BrdU uptake, are incompatible with preservation of cellular viability. Previous studies of HSC proliferation kinetics in vivo have therefore precluded direct functional evaluation of multi-potency and self-renewal, the hallmark properties of HSCs. METHODOLOGY/PRINCIPAL FINDINGS: We developed a non-invasive labeling technique that allowed us to identify and isolate candidate HSCs and early hematopoietic progenitor cells based on their differential in vivo proliferation kinetics. Such cells were functionally evaluated for their abilities to multi-lineage reconstitute myeloablated hosts. CONCLUSIONS: Although at least a few HSC divisions per se did not influence HSC function, enhanced kinetics of divisional activity in steady state preceded the phenotypic changes that accompanied loss of HSC self-renewal. Therefore, mitotic quiescence of HSCs, relative to their committed progeny, is key to maintain the unique functional and molecular properties of HSCs.

Place, publisher, year, edition, pages
San Francisco: Public Library of Science , 2008. Vol. 3, no 11, art. no. e3710- p.
Keyword [en]
Animals, Biological Assay, Cell Differentiation, Cell Division, Cell Lineage, Cell Proliferation, Cultured Cells, Gene Expression Profiling, Hematopoietic Stem Cells, Kinetics, Mice, Inbred C57BL Mice, Biological Models
National Category
Medical and Health Sciences
URN: urn:nbn:se:hh:diva-15168DOI: 10.1371/journal.pone.0003710ISI: 000265166000010PubMedID: 19002266ScopusID: 2-s2.0-56649121821OAI: diva2:419606
Available from: 2011-05-27 Created: 2011-05-27 Last updated: 2015-09-21Bibliographically approved

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