Twenty years ago, a paper appeared that catalyzed the emergence of a field. Schmitt and Zúñiga-Pflücker (1) 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...

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