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Precise developmental regulation of Ets family transcription factors during specification and commitment to the T cell lineage

Anderson, Michele K. and Hernandez-Hoyos, Gabriela and Diamond, Rochelle A. and Rothenberg, Ellen V. (1999) Precise developmental regulation of Ets family transcription factors during specification and commitment to the T cell lineage. Development, 126 (14). pp. 3131-3148. ISSN 0950-1991.

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Ets family transcription factors control the expression of a large number of genes in hematopoietic cells. Here we show strikingly precise differential expression of a subset of these genes marking critical, early stages of mouse lymphocyte cell-type specification. Initially, the Ets family member factor Erg was identified during an arrayed cDNA library screen for genes encoding transcription factors expressed specifically during T cell lineage commitment. Multiparameter fluorescence-activated cell sorting for over a dozen cell surface markers was used to isolate 18 distinct primary-cell populations representing discrete T cell and B cell developmental stages, pluripotent lymphoid precursors, immature NK-like cells and myeloid hematopoietic cells. These populations were monitored for mRNA expression of the Erg, Ets-1, Ets-2, Fli-1, Tel, Elf-1, GABPalpha, PU.1 and Spi-B genes. The earliest stages in T cell differentiation show particularly dynamic Ets family gene regulation, with sharp transitions in expression correlating with specification and commitment events. Ets, Spi-B and PU.1 are expressed in these stages but not by later T-lineage cells. Erg is induced during T-lineage specification and then silenced permanently, after commitment, at the beta-selection checkpoint. Spi-B is transiently upregulated during commitment and then silenced at the same stage as Erg. T-lineage commitment itself is marked by repression of PU.1, a factor that regulates B-cell and myeloid genes. These results show that the set of Ets factors mobilized during T-lineage specification and commitment is different from the set that maintains T cell gene expression during thymocyte repertoire selection and in all classes of mature T cells.

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Rothenberg, Ellen V.0000-0002-3901-347X
Additional Information:© 1999 The Company of Biologists Limited. Accepted 27 April; published on WWW 21 June 1999. The authors would like to thank Hua Wang and Susannah Barbee for generous donations of several sorted cell samples and the other members of the laboratory for helpful discussions. We are grateful to Dr Ellen Robey for providing the MHC-deficient mice, to Ted Biondi and Leanne Rochanda for valuable help with the Q-BOT arraying robot, to Patrick Koen of the Caltech Flow Cytometry/Cell Sorting Facility for excellent assistance with the cell sorting, to the Caltech Biopolymer Synthesis Facility for providing numerous high-quality oligonucleotides, and to the Caltech Sequencing Facility for expeditious sequence analysis. We would also like to thank Eric Davidson and Jonathan Rast for critical reading and thoughtful comments on the manuscript. This work was supported by the Stowers Institute for Medical Research and by USPHS grants AI34041 and AG13108.
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Stowers Institute for Medical ResearchUNSPECIFIED
Subject Keywords:T cell development; Ets family; gene expression; hematopoiesis
Issue or Number:14
Record Number:CaltechAUTHORS:20120109-142434194
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Official Citation:Precise developmental regulation of Ets family transcription factors during specification and commitment to the T cell lineage M.K. Anderson, G. Hernandez-Hoyos, R.A. Diamond, E.V. Rothenberg Development 1999 126: 3131-3148
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:28717
Deposited By: Tony Diaz
Deposited On:11 Jan 2012 19:16
Last Modified:03 Oct 2019 03:35

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