Linked Life Data

17823311

Source:http://linkedlifedata.com/resource/pubmed/id/17823311

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2007-10-16
pubmed:abstractText
Studies of HIV-1-infected individuals on anti-retroviral therapies and of patients receiving lymphoablating treatments indicate that the thymus retains restorative capacity even in adults. The contributions of the thymic epithelial cells (TECs) to the regeneration of the thymus and the identity of epithelial cell progenitors were evaluated in murine models of transient thymic atrophy followed by a complete regeneration. Using microarray approach, we analyzed the pattern of gene expression in TECs sorted from mice that were depleted of thymocytes by steroid treatment or by irradiation. The initial analysis identified significant increases in the mRNA for cMyc, Trp63 and Tcf3 transcription factors known to be expressed in early epithelial cell progenitors in tissues other than the thymus. Immunohistochemistry showed that in involuted thymuses, the cMyc and Trp63 proteins were expressed in a subset of cortical thymic epithelial cells (cTECs) that were keratin 5 positive (K5(+)), typifying cTEC precursors. Importantly, confocal microscopy established that epithelial cells with the phenotype of putative TEC progenitors (i.e. K5(+)K8(+)) expressed the Trp63 protein and confirmed that K5(+)K8(+) TEC progenitors expanded significantly during atrophy and prior to the thymic regeneration. Thus, our data demonstrated for the first time that critical steps in the recovery of the adult thymus include expansion of TEC progenitors and elevated expression of Trp63, cMyc and Tcf3 transcription factors in the thymic stroma. These results suggest that TEC progenitors could be reactivated in the adult thymus and, therefore, reactivation of TEC progenitors could provide a new approach for thymic reconstitution.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0953-8178
pubmed:author
pubmed:issnType
Print
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1249-60
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:17823311-Animals, pubmed-meshheading:17823311-Dexamethasone, pubmed-meshheading:17823311-Epithelial Cells, pubmed-meshheading:17823311-Female, pubmed-meshheading:17823311-Gamma Rays, pubmed-meshheading:17823311-Gene Expression, pubmed-meshheading:17823311-Genes, myc, pubmed-meshheading:17823311-Mice, pubmed-meshheading:17823311-Mice, Inbred BALB C, pubmed-meshheading:17823311-Phosphoproteins, pubmed-meshheading:17823311-Proto-Oncogene Proteins c-myc, pubmed-meshheading:17823311-Stem Cells, pubmed-meshheading:17823311-TCF Transcription Factors, pubmed-meshheading:17823311-Thymus Gland, pubmed-meshheading:17823311-Trans-Activators, pubmed-meshheading:17823311-Transcription Factor 7-Like 1 Protein, pubmed-meshheading:17823311-Transcription Factors, pubmed-meshheading:17823311-Up-Regulation
pubmed:year
2007
pubmed:articleTitle
Regeneration of the adult thymus is preceded by the expansion of K5+K8+ epithelial cell progenitors and by increased expression of Trp63, cMyc and Tcf3 transcription factors in the thymic stroma.
pubmed:affiliation
Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, 8800 Rockville Pike, Bethesda, MD 20892, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't