Open AccessCCAAT/Enhancer‐Binding Protein β Expressed by Bone Marrow Mesenchymal Stromal Cells Regulates Early B‐Cell Lymphopoiesis
Author(s) -
Yoshioka Satoshi,
Miura Yasuo,
Yao Hisayuki,
Satake Sakiko,
Hayashi Yoshihiro,
Tamura Akihiro,
Hishita Terutoshi,
Ichinohe Tatsuo,
Hirai Hideyo,
Takaor-Kondo Akifumi,
Maekawa Taira
Publication year - 2014
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1555
Subject(s) - bone marrow , lymphopoiesis , stromal cell , biology , ccaat enhancer binding proteins , haematopoiesis , mesenchymal stem cell , microbiology and biotechnology , population , stem cell , immunology , b cell , cancer research , transcription factor , biochemistry , antibody , medicine , dna binding protein , environmental health , gene
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. S tem C ells 2014;32:730–740