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Lineage plasticity and commitment in T-cell development

Rothenberg, Ellen V. and Dionne, Christopher J. (2002) Lineage plasticity and commitment in T-cell development. Immunological Reviews, 187 (1). pp. 96-115. ISSN 0105-2896. doi:10.1034/j.1600-065X.2002.18709.x.

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The earliest stages of intrathymic T-cell development include not only the acquisition of T-cell characteristics but also programmed loss of potentials for B, natural killer, and dendritic cell development. Evidence from genetics and cell-transfer studies suggests an order and some components of the mechanisms involved in loss of these options, but some of the interpretations conflict. The conflicts can be resolved by a view that postulates overlapping windows of developmental opportunity and individual mechanisms regulating progression along each pathway. This view is consistent with molecular evidence for the expression patterns of positive regulators of non-T developmental pathways, SCL, PU.1 and Id2, in early thymocytes. To some extent, overexpression of such regulators redirects thymocyte development in vitro. Specific commitment functions may normally terminate this developmental plasticity. Both PU.1 overexpression and stimulation of ectopically expressed growth factor receptors can perturb T- and myeloid/dendritic-cell divergence, but only in permissive stages. A cell-line system that approximates DN3-stage thymocytes reveals that PU.1 can alter specification even in a homogeneous population. However, the response of the population to PU.1 is sharply discontinuous. These studies show a critical role for regulatory context in restricting plasticity, which is probably maintained by interacting transcription factor networks.

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Rothenberg, Ellen V.0000-0002-3901-347X
Additional Information:© 2002 Blackwell Munksgaard. Issue online: 4 October 2002; Version of record online: 4 October 2002. We thank Drs Michael Carleton and David Wiest for generously donating the SCID.adh cell line to us, and Drs Hergen Spits, Garry Nolan, and David Rawlings who provided us with the LZRS retroviral vector system. We also thank Dr T. S. Ramalingam for help using the confocal microscope. This work was greatly stimulated by discussions with Drs H. Robson MacDonald, Hergen Spits, Harinder Singh, Yoshimoto Katsura, Hans-Reimer Rodewald, Kenneth Dorshkind, and Irving Weissman that are a pleasure to acknowledge even when our interpretations differ. We are grateful to Dr Michele Anderson for critical reading of this manuscript. We also thank Drs Michele Anderson and Mary Yui, and Hua Wang and Rochelle Diamond, in this laboratory for permission to cite their unpublished results. Relevant work in the Rothenberg laboratory was supported by grants from the USPHS (CA92033, AG13108), NSF (MCB-9983129) and NASA (NAG2-1370), after being initiated under the sponsorship of the Stowers Institute for Medical Research. C.J.D. was supported by a predoctoral training grant from the NIH, 5T32 GM07616.
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Stowers Institute for Medical ResearchUNSPECIFIED
NIH Predoctoral Fellowship5T32 GM07616
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Record Number:CaltechAUTHORS:20170208-153410241
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Official Citation:Rothenberg, E. V. and Dionne, C. J. (2002), Lineage plasticity and commitment in T-cell development. Immunological Reviews, 187: 96–115. doi:10.1034/j.1600-065X.2002.18709.x
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:74175
Deposited By: Tony Diaz
Deposited On:08 Feb 2017 23:45
Last Modified:11 Nov 2021 05:25

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