Document Detail


Asymmetric chromatid segregation in cardiac progenitor cells is enhanced by Pim-1 kinase.
MedLine Citation:
PMID:  22441844     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
RATIONALE: Cardiac progenitor cells (CPCs) in the adult heart are used for cell-based treatment of myocardial damage, but factors determining stemness, self-renewal, and lineage commitment are poorly understood. Immortal DNA strands inherited through asymmetric chromatid segregation correlate with self-renewal of adult stem cells, but the capacity of CPCs for asymmetric segregation to retain immortal strands is unknown. Cardioprotective kinase Pim-1 increases asymmetric cell division in vivo, but the ability of Pim-1 to enhance asymmetric chromatid segregation is unknown.
OBJECTIVE: We aimed to demonstrate immortal strand segregation in CPCs and the enhancement of asymmetric chromatid distribution by Pim-1 kinase.
METHODS AND RESULTS: Asymmetric segregation is tracked by incorporation of bromodeoxyuridine. The CPC DNA was labeled for several generations and then blocked in second cytokinesis during chase to determine distribution of immortal versus newly synthesized strands. Intensity ratios of binucleated CPCs with bromodeoxyuridine of ≥70:30 between daughter nuclei indicative of asymmetric chromatid segregation occur with a frequency of 4.57, and asymmetric chromatid segregation is demonstrated at late mitotic phases. Asymmetric chromatid segregation is significantly enhanced by Pim-1 overexpression in CPCs (9.19 versus 4.79 in eGFP-expressing cells; P=0.006).
CONCLUSIONS: Asymmetric segregation of chromatids in CPCs is increased nearly two-fold with Pim-1 kinase overexpression, indicating that Pim-1 promotes self-renewal of stem cells.
Authors:
Balaji Sundararaman; Daniele Avitabile; Mathias H Konstandin; Christopher T Cottage; Natalie Gude; Mark A Sussman
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-03-22
Journal Detail:
Title:  Circulation research     Volume:  110     ISSN:  1524-4571     ISO Abbreviation:  Circ. Res.     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-04-27     Completed Date:  2012-06-22     Revised Date:  2014-04-15    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1169-73     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Bromodeoxyuridine / metabolism
Cell Proliferation*
Cells, Cultured
Chromatids / metabolism*
Chromosome Segregation*
Cytokinesis
DNA Replication
Green Fluorescent Proteins / genetics,  metabolism
Humans
Mice
Mitosis*
Myocytes, Cardiac / enzymology*
Proto-Oncogene Proteins c-pim-1 / genetics,  metabolism*
Stem Cells / enzymology*
Transfection
Grant Support
ID/Acronym/Agency:
1 R21 HL102613-02/HL/NHLBI NIH HHS; 1 R21 HL104544-02/HL/NHLBI NIH HHS; 1 R21HL102714-02/HL/NHLBI NIH HHS; 1R21HL102714-01/HL/NHLBI NIH HHS; 2 R01 HL067245/HL/NHLBI NIH HHS; 5P01HL085577-05/HL/NHLBI NIH HHS; IR37 HL091102-01/HL/NHLBI NIH HHS; P01 HL085577-05/HL/NHLBI NIH HHS; R01 HL067245/HL/NHLBI NIH HHS; R01 HL067245-10/HL/NHLBI NIH HHS; R01 HL105759/HL/NHLBI NIH HHS; R01 HL105759-01/HL/NHLBI NIH HHS; R01 HL105759-03/HL/NHLBI NIH HHS; R01 HL113656/HL/NHLBI NIH HHS; R21 HL102613-02/HL/NHLBI NIH HHS; R21 HL102714-02/HL/NHLBI NIH HHS; R21 HL104544-02/HL/NHLBI NIH HHS; R37 HL091102/HL/NHLBI NIH HHS; R37 HL091102-05/HL/NHLBI NIH HHS; RC1HL100891-02/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/enhanced green fluorescent protein; 147336-22-9/Green Fluorescent Proteins; EC 2.7.11.1/PIM1 protein, human; EC 2.7.11.1/Proto-Oncogene Proteins c-pim-1; G34N38R2N1/Bromodeoxyuridine
Comments/Corrections
Comment In:
Circ Res. 2012 Apr 27;110(9):1154-6   [PMID:  22539751 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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