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PMID: 16479167 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

The GOD of hematopoietic stem cells: a clonal diversity model of the stem cell compartment.

Cell cycle (Georgetown, Tex.) ·Vol. 5 ·No. 4 ·2006-02-00 ·Pages 394-8

Muller-Sieburg CE, Sieburg HB

Abstract

Hematopoietic stem cells (HSC) show heterogeneous behavior even when isolated as phenotypically homogeneous populations. The cellular and molecular mechanisms that control the generation of diversity (GOD) in the HSC compartment are not well understood, but have been the focus of much debate. There is increasing evidence that the most important HSC functions, self-renewal and differentiation, are epigenetically preprogrammed and therefore predictable. Indeed, recent data show that the adult HSC compartment consists of a limited number of functionally distinct subsets of HSC. This contradicts older models of HSC behavior, which postulated a single type of HSC that can be continuously molded into different subtypes of HSC. We propose a clonal diversity model where the adult HSC compartment consists of a fixed number of different types of HSC, each with epigenetically preprogrammed behavior. Aging or disease may change the overall function of the HSC population. The model predicts that these changes reflect the relative composition of the HSC subsets, rather than changes in individual HSC. This view has implications for using HSC in experimental and clinical settings. Selection for the appropriate subsets of HSC, rather than attempts to force HSC to adjust, should improve their utility in transplantation and gene transfer applications.

MeSH Terms
Animals Cell Compartmentation Cell Differentiation/genetics Cell Lineage Clone Cells/cytology Epigenesis, Genetic Hematopoietic Stem Cells/cytology,metabolism Models, Biological
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Muller-Sieburg C E
Sidney Kimmel Cancer Center, San Diego, California 92112, USA. [email protected]
Sieburg H B
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Article Info
Journal
Cell cycle (Georgetown, Tex.)
Abbr.
Cell Cycle
ISSN
1551-4005
DOI
10.4161/cc.5.4.2487
Email
[email protected]
Published
2006-02-00
Epub
2006-00-15
Pages
394-8
Language
English
Region
United States
NLM ID
101137841
PMCID
PMC1464375
Subset
IM
Grants
NIA NIH HHS · AG023197 · United States
NIA NIH HHS · R01 AG023197 · United States
NIDDK NIH HHS · R01 DK048015 · United States
NIDDK NIH HHS · DK48015 · United States
NIDDK NIH HHS · R56 DK048015 · United States
External Links
PubMed source DOI: 10.4161/cc.5.4.2487 PMC Full Text View journal details
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