Analysis of Transcription Factor Expression during Discrete Stages of Postnatal Thymocyte Differentiation

Abstract

Postnatal T lymphocyte differentiation in the thymus is a multistage process involving serial waves of lineage specification, proliferative expansion, and survival/cell death decisions. Although these are believed to originate from signals derived from various thymic stromal cells, the ultimate consequence of these signals is to induce the transcriptional changes that are definitive of each step. To help to characterize this process, high density microarrays were used to analyze transcription factor gene expression in RNA derived from progenitors at each stage of T lymphopoietic differentiation, and the results were validated by a number of appropriate methods. We find a large number of transcription factors to be expressed in developing T lymphocytes, including many with known roles in the control of differentiation, proliferation, or cell survival/death decisions in other cell types. Some of these are expressed throughout the developmental process, whereas others change substantially at specific developmental transitions. The latter are particularly interesting, because stage-specific changes make it increasingly likely that the corresponding transcription factors may be involved in stage-specific processes. Overall, the data presented here represent a large resource for gene discovery and for confirmation of results obtained through other methods.

Wnt signaling in the thymus is regulated by differential expression of intracellular signaling molecules

“…Microarray studies of the murine thymocyte subsets have been performed by Petrie and coworkers (19). By mining these data for thymic Wnt target genes, we found that p150,95, fos, and jun were expressed at high levels at the DN1 stage and rapidly decreased in the more mature stages (Fig.…”

Developmental Stage-Specific Regulation of TCR-α-Chain Gene Assembly by Intrinsic Features of the TEA Promoter

“…However, it is also possible that some additional trans-acting factors are required for TEA activity but are only expressed in DP thymocytes. In this regard, it is notable that the expression of Ets family transcription factors, which are predicted to bind to the TEA promoter, are up-regulated as cells transit from the DN to the DP stage of thymocyte development (24). It is also possible that the TEA promoter has a 5Ј region with insulator activity.…”

T‐Cell lymphoblastic lymphoma presenting as bilateral multinodular breast masses: A case report and review of the literature

“…Commonly occurring translocations juxtapose the regulatory regions of TCR genes, located at chromosomes 14q11, 7q32-36, and 7p15, with proto-oncogenes, usually transcription factors, that include Tal1, Tal2, Lyl1, Lom2, and Lck [4]. Intriguingly, some of these transcription factors are expressed in early (DN) thymocytes [39], and the oncogenic fusion transcripts are thought to cause dysregulated growth and maturation arrest of the lymphoblasts. Other chromosomal translocations, not involving the TCR genes, were also reported in T-LBL [40,41].…”