Linked Life Data

19690340

Source:http://linkedlifedata.com/resource/pubmed/id/19690340

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
2009-10-16
pubmed:abstractText
Molecular mechanisms preserving hematopoietic stem cell (HSC) self-renewal by maintaining a balance between proliferation, differentiation, and other processes are not fully understood. Hyperactivation of the mammalian target of rapamycin (mTOR) pathway, causing sustained proliferative signals, can lead to exhaustion of HSC repopulating ability. We examined the role of the novel ras gene Rheb2, an activator of the mTOR kinase, in colony-forming ability, survival, and repopulation of immature mouse hematopoietic cells. In a cell line model of mouse hematopoietic progenitor cells (HPCs), we found enhanced proliferation and mTOR signaling in cells overexpressing Rheb2. In addition, overexpression of Rheb2 enhanced colony-forming ability and survival of primary mouse bone marrow HPCs. Expansion of phenotypic HSCs in vitro was enhanced by Rheb2 overexpression. Consistent with these findings, Rheb2 overexpression transiently expanded phenotypically defined immature hematopoietic cells after in vivo transplantation; however, these Rheb2-transduced cells were significantly impaired in overall repopulation of primary and secondary congenic transplantation recipients. Our findings suggest that HPCs and HSCs behave differently in response to growth-promoting signals stimulated by Rheb2. These results may have value in elucidating mechanisms controlling the balance between proliferation and repopulating ability, a finding of importance in clinical uses of HPCs/HSCs.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1528-0020
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
114
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3392-401
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:19690340-Animals, pubmed-meshheading:19690340-Carrier Proteins, pubmed-meshheading:19690340-Cell Line, pubmed-meshheading:19690340-Cell Proliferation, pubmed-meshheading:19690340-Cell Survival, pubmed-meshheading:19690340-Gene Expression, pubmed-meshheading:19690340-Hematopoietic Stem Cell Transplantation, pubmed-meshheading:19690340-Hematopoietic Stem Cells, pubmed-meshheading:19690340-Humans, pubmed-meshheading:19690340-Mice, pubmed-meshheading:19690340-Models, Biological, pubmed-meshheading:19690340-Monomeric GTP-Binding Proteins, pubmed-meshheading:19690340-Neuropeptides, pubmed-meshheading:19690340-Phosphotransferases (Alcohol Group Acceptor), pubmed-meshheading:19690340-Signal Transduction, pubmed-meshheading:19690340-TOR Serine-Threonine Kinases, pubmed-meshheading:19690340-Transplantation, Homologous
pubmed:year
2009
pubmed:articleTitle
Overexpression of Rheb2 enhances mouse hematopoietic progenitor cell growth while impairing stem cell repopulation.
pubmed:affiliation
Department of Microbiology and Immunology, Indiana University School of Medicine, Walther Oncology Center, Indianapolis, IN 46202-5181, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural