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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.

Nygren, Jens LU and Bryder, David LU (2008) In PLoS One 3(11).
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS One
volume
3
issue
11
publisher
Public Library of Science
external identifiers
  • WOS:000265166000010
  • PMID:19002266
  • Scopus:56649121821
ISSN
1932-6203
DOI
10.1371/journal.pone.0003710
language
English
LU publication?
yes
id
f3a40794-86bf-452b-b4d6-ecf46ee78b25 (old id 1271567)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19002266?dopt=Abstract
date added to LUP
2008-12-04 15:04:48
date last changed
2016-10-13 10:41:40
@misc{f3a40794-86bf-452b-b4d6-ecf46ee78b25,
  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.},
  author       = {Nygren, Jens and Bryder, David},
  issn         = {1932-6203},
  language     = {eng},
  number       = {11},
  publisher    = {ARRAY(0x91f02f8)},
  series       = {PLoS One},
  title        = {A novel assay to trace proliferation history in vivo reveals that enhanced divisional kinetics accompany loss of hematopoietic stem cell self-renewal.},
  url          = {http://dx.doi.org/10.1371/journal.pone.0003710},
  volume       = {3},
  year         = {2008},
}