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Mast cell lineage diversion of T lineage precursors by the essential T cell transcription factor GATA-3

Taghon, Tom and Yui, Mary A. and Rothenberg, Ellen V. (2007) Mast cell lineage diversion of T lineage precursors by the essential T cell transcription factor GATA-3. Nature Immunology, 8 (8). pp. 845-855. ISSN 1529-2908. PMCID PMC3140173. doi:10.1038/ni1486.

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GATA-3 is essential for T cell development from the earliest stages. However, abundant GATA-3 can drive T lineage precursors to a non–T cell fate, depending on Notch signaling and developmental stage. Here, overexpression of GATA-3 blocked the survival of pro–T cells when Notch-Delta signals were present but enhanced viability in their absence. In fetal thymocytes at the double-negative 1 (DN1) stage and DN2 stage but not those at the DN3 stage, overexpression of GATA-3 rapidly induced respecification to the mast cell lineage with high frequency by direct transcriptional 'reprogramming'. Normal DN2 thymocytes also showed mast cell potential when interleukin 3 and stem cell factor were added in the absence of Notch signaling. Our results suggest a close relationship between the pro–T cell and mast cell programs and a previously unknown function for Notch in T lineage fidelity.

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Yui, Mary A.0000-0002-3136-2181
Rothenberg, Ellen V.0000-0002-3901-347X
Additional Information:© 2007 Nature Publishing Group. Received 17 April; accepted 11 June; published online 1 July 2007. We thank S.L. Adams and D. Perez for assistance in cell sorting; A. Arias for generating early results related to this project; M.K. Anderson, C.C. Tydell and E.-S. David-Fung for primers; R. Diamond for cell separation advice and help with sorting; R. Bayon, N. Bouey and L. del Carmen Sandoval for animal care; P. Koen for cytometry support; R. Butler, N. Feng and G. De Smet for technical assistance; and V. Stove and colleagues (Department of Clinical Chemistry, University of Ghent) and K. Swerts (Department of Pediatric Hematology and Oncology, University of Ghent) for cytospins and microscopic analysis. Supported by the Beckman Institute at Caltech (for the Caltech Flow Cytometry/Cell Sorting Facility), the National Institutes of Health (R01 CA98925 and R01 CA90233 to E.V.R.; R01 AI064590 to M.A.Y.) and the action ‘Return Grants’ of the Belgian Science Policy (T.T.). Author Contributions: T.T., M.A.Y. and E.V.R. designed the experiments, analyzed data and wrote the manuscript; T.T. and M.A.Y. did the research.
Funding AgencyGrant Number
Caltech Beckman InstituteUNSPECIFIED
NIHR01 CA98925
NIHR01 CA90233
NIHR01 AI064590
Belgian Science PolicyUNSPECIFIED
Issue or Number:8
PubMed Central ID:PMC3140173
Record Number:CaltechAUTHORS:20150317-124107825
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:55856
Deposited By: Tony Diaz
Deposited On:17 Mar 2015 21:47
Last Modified:10 Nov 2021 20:51

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