研究会のご案内
リエゾンラボ研究会
発表内容

Title: 
Gene regulatory networks that orchestrate T and B lymphocyte development

 

Tomokatsu Ikawa, Ph.D.
Laboratory for Immune Regeneration, RIKEN Center for Integrative Medical Sciences 

 

Abstract:
T and B cells play a central role in acquired immune system. These lymphocytes are generated from hematopoietic stem cells (HSCs) in bone marrow. Lymphocyte development is regulated by transcription factors (TFs) that control the lineage specific gene programs. Epigenetic regulation also greatly contributes to maintain the differentiating cell fate. Many TFs and epigenetic modifiers were identified as critical factors of lymphocyte development. However, how these TFs act in concert with epigenetic regulators through genetic circuits or how such TFs connect with other TFs among the regulatory networks remains to be determined.
I will talk about two topics of our recent studies in this seminar. For the first part of my talk, I will discuss the epigenetic control of T lymphocyte development, especially focusing on the role of polycomb group proteins in the maintenance of T cell fates. The second topic is about the gene regulatory networks that underlie the cellular identity of B cells. We have recently established the multipotent progenitors that have self-renewal activities and can be easily induced to differentiate into B cells (Ikawa et al. Stem cell reports, 2015). We have examined transcriptome profiles and the histone modification on the transcriptional regulatory regions of the TFs to construct the transcriptional networks in B cell lineage commitment using this system. The dynamic and cascading wave of the TF expression and the close relationship between TFs were disclosed. The regulators with previously unrecognized roles in control of B cell identity were also determined. These findings will provide a blueprint for studying the normal and neoplastic development of HSCs.

 

References
1. Ikawa T, Masuda K, Huijskens MJAJ, Satoh R, Kakugawa K, Agata Y, Miyai T, Germeraad WTV, Katsura Y, and Kawamoto H. Induced developmental arrest of early hematopoietic progenitors leads to the generation of leukocyte stem cells. Stem Cell Reports. 5: 716-727, 2015
2. Ikawa T. Genetic and epigenetic control of early lymphocyte development. Curr Top Microbiol Immunol. 381: 1-20, 2014
3. Ikawa T, Hirose S, Masuda K, Kakugawa K, Satoh R, Shibano-Satoh A, Kominami R, Katsura Y, and Kawamoto H. An essential developmental checkpoint for production of the T cell lineage. Science. 329: 93-96, 2010