Source:http://linkedlifedata.com/resource/pubmed/id/18156489
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
|
| pubmed:dateCreated |
2008-2-26
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| pubmed:abstractText |
The polycomb group (PcG) gene BMI1 has been identified as one of the key epigenetic regulators of cell fates during different stages of development in multiple murine tissues. In a clinically relevant model, we demonstrate that enforced expression of BMI1 in cord blood CD34(+) cells results in long-term maintenance and self-renewal of human hematopoietic stem and progenitor cells. Long-term culture-initiating cell frequencies were increased upon stable expression of BMI1 and these cells engrafted more efficiently in NOD-SCID mice. Week 5 cobblestone area-forming cells (CAFCs) were replated to give rise to secondary CAFCs. Serial transplantation studies in NOD-SCID mice revealed that secondary engraftment was only achieved with cells overexpressing BMI1. Importantly, BMI1-transduced cells proliferated in stroma-free cytokine-dependent cultures for more than 20 weeks, while a stable population of approximately 1% to 5% of CD34(+) cells was preserved that retained colony-forming capacity. Whereas control cells lost most of their NOD-SCID engraftment potential after 10 days of ex vivo culturing in absence of stroma, NOD-SCID multilineage engraftment was retained by overexpression of BMI1. Thus, our data indicate that self-renewal of human hematopoietic stem cells is enhanced by BMI1, and we classify BMI1 as an intrinsic regulator of human stem/progenitor cell self-renewal.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD34,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD38,
http://linkedlifedata.com/resource/pubmed/chemical/BMI1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Mar
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| pubmed:issn |
0006-4971
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
1
|
| pubmed:volume |
111
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
2621-30
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| pubmed:meshHeading |
pubmed-meshheading:18156489-Animals,
pubmed-meshheading:18156489-Antigens, CD34,
pubmed-meshheading:18156489-Antigens, CD38,
pubmed-meshheading:18156489-Apoptosis,
pubmed-meshheading:18156489-Cell Proliferation,
pubmed-meshheading:18156489-Cells, Cultured,
pubmed-meshheading:18156489-Chimerism,
pubmed-meshheading:18156489-Female,
pubmed-meshheading:18156489-Fetal Blood,
pubmed-meshheading:18156489-Hematopoietic Stem Cell Transplantation,
pubmed-meshheading:18156489-Hematopoietic Stem Cells,
pubmed-meshheading:18156489-Humans,
pubmed-meshheading:18156489-Mice,
pubmed-meshheading:18156489-Mice, SCID,
pubmed-meshheading:18156489-Nuclear Proteins,
pubmed-meshheading:18156489-Proto-Oncogene Proteins,
pubmed-meshheading:18156489-Repressor Proteins,
pubmed-meshheading:18156489-Retroviridae,
pubmed-meshheading:18156489-Stromal Cells,
pubmed-meshheading:18156489-Time Factors
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| pubmed:year |
2008
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| pubmed:articleTitle |
Long-term maintenance of human hematopoietic stem/progenitor cells by expression of BMI1.
|
| pubmed:affiliation |
Department of Cell Biology, Section Stem Cell Biology, University Medical Center, University of Groningen, Deusinglaan 1, Groningen, The Netherlands.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|