Document Detail


Alcam regulates long-term hematopoietic stem cell engraftment and self-renewal.
MedLine Citation:
PMID:  23280653     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hematopoietic stem cells (HSCs) reside in a specialized bone marrow (BM) microenvironment that supports the maintenance and functional integrity of long-term (LT)-HSCs throughout postnatal life. The objective of this work is to study the role of activated leukocyte cell adhesion molecule (Alcam) in HSC differentiation and self-renewal using an Alcam-null (Alcam(-/-) ) mouse model. We show here that Alcam is differentially regulated in adult hematopoiesis and is highly expressed in LT-HSCs where its level progressively increases with age. Young adult Alcam(-/-) mice had normal homeostatic hematopoiesis and normal numbers of phenotypic HSCs. However, Alcam(-/-) HSCs had reduced long-term replating capacity in vitro and reduced long-term engraftment potential upon transplantation. We show that Alcam(-/-) BM contain a markedly lower frequency of long-term repopulating cells than wild type. Further, the long-term repopulating potential and engraftment efficiency of Alcam(-/-) LT-HSCs was greatly compromised despite a progressive increase in phenotypic LT-HSC numbers during long-term serial transplantation. In addition, an age-associated increase in phenotypic LT-HSC cellularity was observed in Alcam(-/-) mice. This increase was predominately within the CD150(hi) fraction and was accompanied by significantly reduced leukocyte output. Consistent with an aging-like phenotype, older Alcam(-/-) LT-HSCs display myeloid-biased repopulation activity upon transplantation. Finally, Alcam(-/-) LT-HSCs display premature elevation of age-associated gene expression, including Selp, Clu, Cdc42, and Foxo3. Together, this study indicates that Alcam regulates functional integrity and self-renewal of LT-HSCs.
Authors:
Robin Jeannet; Qi Cai; Hongjun Liu; Hieu Vu; Ya-Huei Kuo
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Stem cells (Dayton, Ohio)     Volume:  31     ISSN:  1549-4918     ISO Abbreviation:  Stem Cells     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-26     Completed Date:  2014-01-07     Revised Date:  2014-03-07    
Medline Journal Info:
Nlm Unique ID:  9304532     Medline TA:  Stem Cells     Country:  United States    
Other Details:
Languages:  eng     Pagination:  560-71     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 AlphaMed Press.
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MeSH Terms
Descriptor/Qualifier:
Activated-Leukocyte Cell Adhesion Molecule / metabolism,  physiology*
Animals
Cell Adhesion / drug effects
Cell Differentiation / physiology
Gene Knockdown Techniques
Hematopoietic Stem Cells / cytology,  metabolism,  physiology*
Mice
Mice, Inbred C57BL
Mice, Knockout
Grant Support
ID/Acronym/Agency:
P30 CA033572/CA/NCI NIH HHS; P30 CA033572/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Activated-Leukocyte Cell Adhesion Molecule
Comments/Corrections

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