Induction of T cell development from hematopoietic progenitor cells by delta-like-1 in vitro.

By Thomas M. Schmitt, J. Zúñiga-Pflücker. Immunity, 2002

1,220 citations recorded by the source corpus.

The molecular interactions provided by the thymic microenvironment that predicate T cell development remain obscure. Here, we show that a bone marrow stromal cell line ectopically expressing the Notch ligand Delta-like-1 loses its ability to support B cell lymphopoiesis, but acquires the capacity to induce the differentiation of hematopoietic progenitors into CD4 CD8 double- and single-positive T cells. Both gammadelta-TCR(+) and alphabeta-TCR(+) T cells are generated, and CD8(+) TCR(hi) cells produce gamma-interferon following CD3/TCR stimulation. These results establish that expression of Delta-like-1 on stromal cells provides key signals for the induction of T cell lineage commitment, stage-specific progenitor expansion, TCR gene rearrangement, and T cell differentiation in the absence of a thymus. Thus, it is likely that Delta-like-1/Notch interactions by the thymus underpin its unique ability to promote lineage commitment and differentiation of T cells.

Subfields: Cell Biology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/47ca4c5a2410f8b74135967beb400cff82c55b6e

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In Cell Biology

1. L. Lanier
2. Joseph C. Sun
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Citations in the corpus

• The role of Notch in tumorigenesis: oncogene or tumour suppressor? (2003, background): “In vitro , a DLL1 signal via Notch drives haematopoietic precursor cells to differentiate into the T-cell lineage, whereas a JAG1 signal prevents differentiation of bone-marrow-progenitor cell”
• Notch regulation of lymphocyte development and function (2004, background): “Delta1 seems to be the essential Notch1 ligand, as stromal cells expressing Delta1 can induce T cell development of human and mouse hematopoietic progenitors in vitro”
• NK cell development, homeostasis and function: parallels with CD8+ T cells (2011, result): “Like with thymocytes, studies using the OP9 stromal cell culture system confirmed that functional NK cells could develop in vitro on stromal cells expressing specific Notch ligands, such as members of the Delta and jagged familie”
• The transcription factor GATA3 controls cell fate and maintenance of type 2 innate lymphoid cells (2012, positive): “See also Figure S3. delta-like 1 (Dll1)-expressing OP9 cells, which is required to generate T cells from uncommitted precursor cells (Schmitt and Zúñiga-Pflücker, 2002).”
• Identification of Flt3+ lympho-myeloid stem cells lacking erythro-megakaryocytic potential a revised road map for adult blood lineage commitment. (2005, methodology): “OP9 and OP9-DL1 cell lines (kindly provided by Drs. A. Cumano, Paris, and J.C. Zuniga Pflucker, Toronto) were maintained as described (Schmitt and Zuniga-Pflucker, 2002; Vieira and Cumano, 2004) in OptiMEM with L-Glutamine (Invitrogen Corporation, Carlsbad, California) supplemented with 10% FCS…”
• Mutational loss of PTEN induces resistance to NOTCH1 inhibition in T-cell leukemia (2007, methodology): “OP9-DL1 and OP9-control cells were generated from the OP9 bone marrow stromal cell line and maintained as describe”