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The Heart of the Machine: Construction of T Cell Identity, Made Accessible

Rothenberg, Ellen V. (2022) The Heart of the Machine: Construction of T Cell Identity, Made Accessible. Journal of Immunology, 209 (7). pp. 1235-1236. ISSN 0022-1767. doi:10.4049/jimmunol.2200264.

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Twenty years ago, a paper appeared that catalyzed the emergence of a field. Schmitt and Zúñiga-Pflücker described a new monolayer-based tissue culture system in which T cell development from hematopoietic precursors could be supported in vitro outside of the thymus. At a stroke, this work resolved debates about key functions of the thymic epithelium, revealed steps in early T cell differentiation with unprecedented precision, allowed T cell lineage commitment to be studied quantitatively, and created an experimental framework for connecting the T cell lineage to the whole range of other hematolymphoid developmental pathways. As subsequent work showed, the system developed by Schmitt and Zúñiga-Pflücker allowed efficient, routine T lineage development from single progenitor cells, enabling rigorous study of cell fate determination at a clonal level. It also opened up the black box of the thymus, enabling genetic perturbation and titration studies that created a foundation for a molecular understanding of the process through which cells enter into the T cell pathway. Even though this system did not go all the way to generate functional mature T cells, it paved the way for work in numerous other laboratories, ultimately helping to make T cell development one of the best understood developmental systems in mammalian biology.

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Rothenberg, Ellen V.0000-0002-3901-347X
Additional Information:Many more authors and many more publications could have been cited here if not for space restrictions, and they are all greatly thanked. E.V.R. gratefully acknowledges support from the Edward B. Lewis Professorship of Biology.
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Edward B. Lewis Professorship of BiologyUNSPECIFIED
Issue or Number:7
Record Number:CaltechAUTHORS:20221104-613497100.22
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:117721
Deposited By: Research Services Depository
Deposited On:17 Nov 2022 19:24
Last Modified:17 Nov 2022 19:24

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