Format

Send to:

Choose Destination
See comment in PubMed Commons below
PLoS One. 2008;3(11):e3710. doi: 10.1371/journal.pone.0003710. Epub 2008 Nov 12.

A novel assay to trace proliferation history in vivo reveals that enhanced divisional kinetics accompany loss of hematopoietic stem cell self-renewal.

Author information

  • 1Stem Cell Aging, Department of Experimental Medical Science, Lund University, Lund, Sweden. jens.nygren@med.lu.se

Abstract

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.

PMID:
19002266
[PubMed - indexed for MEDLINE]
PMCID:
PMC2580029
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Public Library of Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk