Linked Life Data

16951331

Source:http://linkedlifedata.com/resource/pubmed/id/16951331

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2006-9-4
pubmed:abstractText
Notch signaling is critical for T cell development of multipotent hemopoietic progenitors. Yet, how Notch regulates T cell fate specification during early thymopoiesis remains unclear. In this study, we have identified an early subset of CD34high c-kit+ flt3+ IL-7Ralpha+ cells in the human postnatal thymus, which includes primitive progenitors with combined lymphomyeloid potential. To assess the impact of Notch signaling in early T cell development, we expressed constitutively active Notch1 in such thymic lymphomyeloid precursors (TLMPs), or triggered their endogenous Notch pathway in the OP9-Delta-like1 stroma coculture. Our results show that proliferation vs differentiation is a critical decision influenced by Notch at the TLMP stage. We found that Notch signaling plays a prominent role in inhibiting non-T cell differentiation (i.e., macrophages, dendritic cells, and NK cells) of TLMPs, while sustaining the proliferation of undifferentiated thymocytes with T cell potential in response to unique IL-7 signals. However, Notch activation is not sufficient for inducing T-lineage progression of proliferating progenitors. Rather, stroma-derived signals are concurrently required. Moreover, while ectopic IL-7R expression cannot replace Notch for the maintenance and expansion of undifferentiated thymocytes, Notch signals sustain IL-7R expression in proliferating thymocytes and induce IL-7R up-regulation in a T cell line. Thus, IL-7R and Notch pathways cooperate to synchronize cell proliferation and suppression of non-T lineage choices in primitive intrathymic progenitors, which will be allowed to progress along the T cell pathway only upon interaction with an inductive stromal microenvironment. These data provide insight into a mechanism of Notch-regulated amplification of the intrathymic pool of early human T cell progenitors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
177
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3711-20
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16951331-Animals, pubmed-meshheading:16951331-Cell Line, pubmed-meshheading:16951331-Cell Proliferation, pubmed-meshheading:16951331-Cells, Cultured, pubmed-meshheading:16951331-Child, Preschool, pubmed-meshheading:16951331-Growth Inhibitors, pubmed-meshheading:16951331-Humans, pubmed-meshheading:16951331-Infant, pubmed-meshheading:16951331-Infant, Newborn, pubmed-meshheading:16951331-Mice, pubmed-meshheading:16951331-Myeloid Progenitor Cells, pubmed-meshheading:16951331-Organ Culture Techniques, pubmed-meshheading:16951331-Proto-Oncogene Proteins c-kit, pubmed-meshheading:16951331-Receptor, Notch1, pubmed-meshheading:16951331-Receptors, Interleukin-7, pubmed-meshheading:16951331-Signal Transduction, pubmed-meshheading:16951331-T-Lymphocytes, pubmed-meshheading:16951331-Thymus Gland, pubmed-meshheading:16951331-fms-Like Tyrosine Kinase 3
pubmed:year
2006
pubmed:articleTitle
Notch1 and IL-7 receptor interplay maintains proliferation of human thymic progenitors while suppressing non-T cell fates.
pubmed:affiliation
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Madrid, Spain.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't