title: CCAAT/enhancer-binding protein β expressed by bone marrow mesenchymal stromal cells regulates early B-cell lymphopoiesis.
abstract: The transcription factor CCAAT/enhancer-binding protein β (C/EBPβ) regulates the differentiation of a variety of cell types. Here, the role of C/EBPβ expressed by bone marrow mesenchymal stromal cells (BMMSCs) in B-cell lymphopoiesis was examined. The size of the precursor B-cell population in bone marrow was reduced in C/EBPβ-knockout (KO) mice. When bone marrow cells from C/EBPβ-KO mice were transplanted into lethally irradiated wild-type (WT) mice, which provide a normal bone marrow microenvironment, the size of the precursor B-cell population was restored to a level equivalent to that generated by WT bone marrow cells. In coculture experiments, BMMSCs from C/EBPβ-KO mice did not support the differentiation of WT c-Kit(+) Sca-1(+) Lineage(-) hematopoietic stem cells (KSL cells) into precursor B cells, whereas BMMSCs from WT mice did. The impaired differentiation of KSL cells correlated with the reduced production of CXCL12/stromal cell-derived factor-1 by the cocultured C/EBPβ-deficient BMMSCs. The ability of C/EBPβ-deficient BMMSCs to undergo osteogenic and adipogenic differentiation was also defective. The survival of leukemic precursor B cells was poorer when they were cocultured with C/EBPβ-deficient BMMSCs than when they were cocultured with WT BMMSCs. These results indicate that C/EBPβ expressed by BMMSCs plays a crucial role in early B-cell lymphopoiesis.
authors.affiliation: Department of Hematology/Oncology, Graduate School of Medicine, Kyoto University; Department of Transfusion Medicine & Cell Therapy, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yoshioka
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Miura
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Yao
authors.forename: Sakiko
authors.initials: S
authors.lastname: Satake
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tamura
authors.forename: Terutoshi
authors.initials: T
authors.lastname: Hishita
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Ichinohe
authors.forename: Hideyo
authors.initials: H
authors.lastname: Hirai
authors.forename: Akifumi
authors.initials: A
authors.lastname: Takaor-Kondo
authors.forename: Taira
authors.initials: T
authors.lastname: Maekawa
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D001854:Bone Marrow Cells / Q000166:cytology*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000172:deficiency / Q000378:metabolism*; D002454:Cell Differentiation; D002470:Cell Survival; D002478:Cells, Cultured; D060833:Cellular Microenvironment; D054377:Chemokine CXCL12 / Q000096:biosynthesis; D018920:Coculture Techniques; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D015448:Leukemia, B-Cell / Q000473:pathology; D038041:Lymphopoiesis; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010012:Osteogenesis; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D054377:Chemokine CXCL12
keywords: B lymphocytes; Bone marrow; CCAAT/enhancer-binding protein β; Mesenchymal stromal cells