Molecular Dissection of Prethymic Progenitor Entry into the T Lymphocyte Developmental Pathway.
From: Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
Journal of immunology (Baltimore, Md. : 1950)
- Publish Date: Jul 2007
- ISSN: 0022-1767
- Volume: 179
- Issue: 1
- Pages: 421-38
- Medium: Print
- Language: English
- Citation (JAMA): Tydell C Chace, David-Fung Elizabeth-Sharon, Moore Jonathan E, et al. Molecular Dissection of Prethymic Progenitor Entry into the T Lymphocyte Developmental Pathway.. J. Immunol. Jul 2007;179:421-38
Abstract
Notch signaling activates T lineage differentiation from hemopoietic progenitors, but relatively few regulators that initiate this program have been identified, e.g., GATA3 and T cell factor-1 (TCF-1) (gene name Tcf7). To identify additional regulators of T cell specification, a cDNA library from mouse Pro-T cells was screened for genes that are specifically up-regulated in intrathymic T cell precursors as compared with myeloid progenitors. Over 90 genes of interest were identified, and 35 of 44 tested were confirmed to be more highly expressed in T lineage precursors relative to precursors of B and/or myeloid lineage. To a remarkable extent, however, expression of these T lineage-enriched genes, including zinc finger transcription factor, helicase, and signaling adaptor genes, was also shared by stem cells (Lin(-)Sca-1(+)Kit(+)CD27(-)) and multipotent progenitors (Lin(-)Sca-1(+)Kit(+)CD27(+)), although down-regulated in other lineages. Thus, a major fraction of these early T lineage genes are a regulatory legacy from stem cells. The few genes sharply up-regulated between multipotent progenitors and Pro-T cell stages included those encoding transcription factors Bcl11b, TCF-1 (Tcf7), and HEBalt, Notch target Deltex1, Deltex3L, Fkbp5, Eva1, and Tmem131. Like GATA3 and Deltex1, Bcl11b, Fkbp5, and Eva1 were dependent on Notch/Delta signaling for induction in fetal liver precursors, but only Bcl11b and HEBalt were up-regulated between the first two stages of intrathymic T cell development (double negative 1 and double negative 2) corresponding to T lineage specification. Bcl11b was uniquely T lineage restricted and induced by Notch/Delta signaling specifically upon entry into the T lineage differentiation pathway.
Mesh Headings (Keywords): Animals, Cell Differentiation, Cell Lineage, Cells, Cultured, Coculture Techniques, DNA-Binding Proteins, Fetus, Gene Expression Profiling, Hematopoietic Stem Cells, Lymphopoiesis, Membrane Proteins, Mice, Mice, Inbred C57BL, Mice, SCID, Mice, Transgenic, Molecular Sequence Data, Receptors, Notch, Repressor Proteins, Signal Transduction, T-Lymphocyte Subsets, Thymus Gland, Tumor Suppressor Proteins, Up-Regulation
Check for Full Text / PubMed Unique Identifier (PMID): 17579063
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