Journal article
Regulation of early T-lineage gene expression and developmental progression by the progenitor cell transcription factor PU.1
A Champhekar, SS Damle, G Freedman, S Carotta, SL Nutt, EV Rothenberg
Genes and Development | Published : 2015
Abstract
The ETS family transcription factor PU.1 is essential for the development of several blood lineages, including T cells, but its function in intrathymic T-cell precursors has been poorly defined. In the thymus, high PU.1 expression persists through multiple cell divisions in early stages but then falls sharply during T-cell lineage commitment. PU.1 silencing is critical for T-cell commitment, but it has remained unknown how PU.1 activities could contribute positively to T-cell development. Here we employed conditional knockout and modified antagonist PU.1 constructs to perturb PU.1 function stage-specifically in early T cells. We show that PU.1 is needed for full proliferation, restricting ac..
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Awarded by National Institute of Child Health and Human Development
Funding Acknowledgements
We thank Sanket Acharya and Mark Zarnegar for the PU.1-Eng construct; Arthur Skoultchi for related PU.1 constructs used in preliminary studies; Hao Yuan Kueh for discussion on PCA analysis; Jonas Ungerback for sharing unpublished data; Robert Butler and Maria Quiloan for technical assistance; Rochelle Diamond, Diana Perez, and Pat Koen at the Caltech Flow Cytometry and Cell Sorting Facility for cell sorting; Scott Washburn and Ingrid Soto for animal care; and members of E.V.R.'s laboratory for helpful discussions. This work was supported by National Institutes of Health grants (CA90233, AI95943, and HD076915), the Louis A. Garfinkle Memorial Laboratory Fund, the Al Sherman Foundation, and the Albert Billings Ruddock Professorship to E.V.R., and Victorian State Government Operational Infrastructure Support, National Health and Medical Research Council of Australia Independent Research Institute Infrastructure Support grant 361646, Program grant 105492, and Fellowship 1058238 to S.L.N.