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Notch signaling activates T lineage differentiation from hemopoietic progenitors, but relatively few regulators that initiate this program have been identified, e.g., GATA3 and T cell factor-1 (TCF-1) (gene name Tcf7). To identify additional regulators of T cell specification, a cDNA library from mouse Pro-T cells was screened for genes that are specifically up-regulated in intrathymic T cell precursors as compared with myeloid progenitors. Over 90 genes of interest were identified, and 35 of 44 tested were confirmed to be more highly expressed in T lineage precursors relative to precursors of B and/or myeloid lineage. To a remarkable extent, however, expression of these T lineage-enriched genes, including zinc finger transcription factor, helicase, and signaling adaptor genes, was also shared by stem cells (Lin^−Sca-1^+Kit^+CD27^−) and multipotent progenitors (Lin^−Sca-1^+Kit^+CD27^+), although down-regulated in other lineages. Thus, a major fraction of these early T lineage genes are a regulatory legacy from stem cells. The few genes sharply up-regulated between multipotent progenitors and Pro-T cell stages included those encoding transcription factors Bcl11b, TCF-1 (Tcf7), and HEBalt, Notch target Deltex1, Deltex3L, Fkbp5, Eva1, and Tmem131. Like GATA3 and Deltex1, Bcl11b, Fkbp5, and Eva1 were dependent on Notch/Delta signaling for induction in fetal liver precursors, but only Bcl11b and HEBalt were up-regulated between the first two stages of intrathymic T cell development (double negative 1 and double negative 2) corresponding to T lineage specification. Bcl11b was uniquely T lineage restricted and induced by Notch/Delta signaling specifically upon entry into the T lineage differentiation pathway.

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Caltech Authors  

Autor(es)

Tydell, C. C. -  David -  Fung, Elizabeth -  Sharon -  Moore, Jonathan E. -  Rowen, Lee -  Taghon, Tom -  Rothenberg, E. V. - 

Id.: 69634113

Versión: 1.0

Estado: Final

Tipo:  application/pdf - 

Tipo de recurso: Article  -  PeerReviewed  - 

Tipo de Interactividad: Expositivo

Nivel de Interactividad: muy bajo

Audiencia: Estudiante  -  Profesor  -  Autor  - 

Estructura: Atomic

Coste: no

Copyright: sí

Formatos:  application/pdf - 

Requerimientos técnicos:  Browser: Any - 

Relación: [References] http://resolver.caltech.edu/CaltechAUTHORS:20170210-153114201
[References] http://authors.library.caltech.edu/74217/

Fecha de contribución: 12-feb-2017

Contacto:

Localización:
* Tydell, C. C. and David-Fung, Elizabeth-Sharon and Moore, Jonathan E. and Rowen, Lee and Taghon, Tom and Rothenberg, E. V. (2007) Molecular Dissection of Prethymic Progenitor Entry into the T Lymphocyte Developmental Pathway. Journal of Immunology, 179 (1). pp. 421-438. ISSN 0022-1767. http://resolver.caltech.edu/CaltechAUTHORS:20170210-153114201

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