Linked Life Data

20573703

Source:http://linkedlifedata.com/resource/pubmed/id/20573703

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2010-7-14
pubmed:abstractText
Tuberous sclerosis complex human disease gene products TSC1 and TSC2 form a functional complex that negatively regulates target of rapamycin (TOR), an evolutionarily conserved kinase that plays a central role in cell growth and metabolism. Here, we describe a novel role of TSC1/2 in controlling stem cell maintenance. We show that in the Drosophila ovary, disruption of either the Tsc1 or Tsc2 gene in germline stem cells (GSCs) leads to precocious GSC differentiation and loss. The GSC loss can be rescued by treatment with TORC1 inhibitor rapamycin, or by eliminating S6K, a TORC1 downstream effecter, suggesting that precocious differentiation of Tsc1/2 mutant GSC is due to hyperactivation of TORC1. One well-studied mechanism for GSC maintenance is that BMP signals from the niche directly repress the expression of a differentiation-promoting gene bag of marbles (bam) in GSCs. In Tsc1/2 mutant GSCs, BMP signalling activity is downregulated, but bam expression is still repressed. Moreover, Tsc1 bam double mutant GSCs could differentiate into early cystocytes, suggesting that TSC1/2 controls GSC differentiation via both BMP-Bam-dependent and -independent pathways. Taken together, these results suggest that TSC prevents precocious GSC differentiation by inhibiting TORC1 activity and subsequently differentiation-promoting programs. As TSC1/2-TORC1 signalling is highly conserved from Drosophila to mammals, it could have a similar role in controlling stem cell behaviour in mammals, including humans.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1477-9129
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
137
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2461-9
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:20573703-Animals, pubmed-meshheading:20573703-Apoptosis, pubmed-meshheading:20573703-Bone Morphogenetic Proteins, pubmed-meshheading:20573703-Cell Cycle Proteins, pubmed-meshheading:20573703-Cell Differentiation, pubmed-meshheading:20573703-Crosses, Genetic, pubmed-meshheading:20573703-Drosophila Proteins, pubmed-meshheading:20573703-Drosophila melanogaster, pubmed-meshheading:20573703-Germ Cells, pubmed-meshheading:20573703-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:20573703-Microscopy, Fluorescence, pubmed-meshheading:20573703-Models, Biological, pubmed-meshheading:20573703-Mutation, pubmed-meshheading:20573703-Protein-Serine-Threonine Kinases, pubmed-meshheading:20573703-Sirolimus, pubmed-meshheading:20573703-Stem Cells, pubmed-meshheading:20573703-TOR Serine-Threonine Kinases
pubmed:year
2010
pubmed:articleTitle
TSC1/2 tumour suppressor complex maintains Drosophila germline stem cells by preventing differentiation.
pubmed:affiliation
Graduate program, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't