Mast cell lineage diversion of T lineage precursors by the essential T cell transcription factor GATA-3

Tom Taghon, et al. 2007. Nature Immunology 8, 845-855

Speaker: Yi-Wen Tsai (蔡宜文)                                      Time: 14:00~15:00, Oct. 17, 2007

Commentator: Dr. Pin Ling (凌 斌 博士)                      Place: Room 601

Abstract:

    The transcription factor GATA-3 is essential for T cell differentiation and development from the earliest stages. When Notch-Delta signaling triggers T lineage differentiation from hematopoietic precursors, Gata3 is among the earliest regulatory genes induced. However, high dose of GATA-3 blocks cell cycle and can be anti-proliferative in various T lineage cells. Furthermore, some previous studies suggest that GATA-3 does not specifically instruct cells to adopt T lineage identity, but only supports T cell development when expressed in a specific regulatory context. Here, the author tried to determine what instructive effects GATA-3 may have on developing prethymic and intrathymic lymphoid precursors. They noted that overexpressed GATA-3 was not sufficient for initiation of the T lineage with Notch signaling in prethymic precursors, but promoted intrathymic precursor survival without Notch-DL1. Besides, they found in the absence of Notch-DL1, GATA-3-transduced thymocytes contained a subset similar to c-Kit⁺FceRIa⁺ bone marrow-derived mast cells (BMMCs) with expression of very high c-Kit but not Thy-1 and CD27. They also proved that the mast cell lineage diversion associated with overexpressed GATA-3 is common in the double negative 2 (DN2) and DN1 thymocyte population. At last, they demonstrated that DN2 thymocyte with unmanipulated GATA-3 expression also showed mast cell potential in the mast cell condition without Notch-DL1. From this study, they elucidate a previously unknown aspect of the T lineage-commitment process and show a close relationship between the pro-T cell and mast cell developmental programs.

References:

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2. Chen, D. & Zhang, G. Enforced expression of the GATA-3 transcription factor affects cell fate decisions in hematopoiesis. Exp. Hematol. 29, 971–980 (2001). 

3. Taghon, T. et al. Enforced expression of GATA-3 severely reduces human thymic cellularity. J. Immunol. 167, 4468–4475 (2001).