Discovery of protein associated with the aging of the immune system
In cooperation with KONDO Motonari , Professor, Immunology, School of Medicine, Toho University, Dr. Paul Kincade , Oklahoma Medical Research Foundation, USA, Terumi Kohwi-Shigematsu , Professor, University of California, Berkeley, USA, YOKOTA Takafumi , Assistant professor, and SATO Yusuke *, Assistant Professor, Internal Medicine Course, Graduate School of Medicine, Osaka University, a group of researchers found that in blood-forming stem cells, a special AT-rich sequence binding protein 1 (Satb1) regulating nuclear chromatin architecture, declined with age.
This group also found that expression of Satb1 in blood-forming stem cell isolated from the bone marrow of old mice partially restored the ability to produce lymphocytes. This group's achievement will contribute to the development of new technology to increase the level of vaccination effectiveness in the elderly and the activation of immune response to cancer and infectious diseases.
Abstract
How hematopoietic stem cells (HSCs) produce particular lineages is insufficiently understood. We searched for key factors that direct HSC to lymphopoiesis. Comparing gene expression profiles for HSCs and early lymphoid progenitors revealed that Satb1, a global chromatin regulator, was markedly induced with lymphoid lineage specification. HSCs from Satb1-deficient mice were defective in lymphopoietic activity in culture and failed to reconstitute T lymphopoiesis in wild-type recipients. Furthermore, Satb1 transduction of HSCs and embryonic stem cells robustly promoted their differentiation toward lymphocytes. Whereas genes that encode Ikaros, E2A, and Notch1 were unaffected, many genes involved in lineage decisions were regulated by Satb1. Satb1 expression was reduced in aged HSCs with compromised lymphopoietic potential, but forced Satb1 expression partly restored that potential. Thus, Satb1 governs the initiating process central to the replenishing of lymphoid lineages. Such activity in lymphoid cell generation may be of clinical importance and useful to overcome immunosenescence.
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To learn more about this research, please read the full research report entitled " The Satb1 Protein Directs Hematopoietic Stem Cell Differentiation toward Lymphoid Lineages " at this page of the Immunity website.
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* SATO Yusuke is currently, Associate Professor, School of Human Sciences, Kobe Shoin Women's University.
