title: The Satb1 protein directs hematopoietic stem cell differentiation toward lymphoid lineages.
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.
authors.affiliation: Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Satoh
authors.forename: Takafumi
authors.initials: T
authors.lastname: Yokota
authors.forename: Takao
authors.initials: T
authors.lastname: Sudo
authors.forename: Motonari
authors.initials: M
authors.lastname: Kondo
authors.forename: Anne
authors.initials: A
authors.lastname: Lai
authors.forename: Paul W
authors.initials: PW
authors.lastname: Kincade
authors.forename: Taku
authors.initials: T
authors.lastname: Kouro
authors.forename: Ryuji
authors.initials: R
authors.lastname: Iida
authors.forename: Koichi
authors.initials: K
authors.lastname: Kokame
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Miyata
authors.forename: Yoko
authors.initials: Y
authors.lastname: Habuchi
authors.forename: Keiko
authors.initials: K
authors.lastname: Matsui
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Tanaka
authors.forename: Itaru
authors.initials: I
authors.lastname: Matsumura
authors.forename: Kenji
authors.initials: K
authors.lastname: Oritani
authors.forename: Terumi
authors.initials: T
authors.lastname: Kohwi-Shigematsu
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Kanakura
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics; D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D038041:Lymphopoiesis / Q000235:genetics; D036961:Matrix Attachment Region Binding Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000502:physiology*; D019076:Transgenes / Q000235:genetics
chemical_list: D036961:Matrix Attachment Region Binding Proteins; C469541:Satb1 protein, mouse