TY - JOUR
T1 - CCAAT/enhancer-binding protein β expressed by bone marrow mesenchymal stromal cells regulates early B-cell lymphopoiesis
AU - Yoshioka, Satoshi
AU - Miura, Yasuo
AU - Yao, Hisayuki
AU - Satake, Sakiko
AU - Hayashi, Yoshihiro
AU - Tamura, Akihiro
AU - Hishita, Terutoshi
AU - Ichinohe, Tatsuo
AU - Hirai, Hideyo
AU - Takaor-Kondo, Akifumi
AU - Maekawa, Taira
N1 - Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 2014/3
Y1 - 2014/3
N2 - 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.
AB - 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.
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U2 - 10.1002/stem.1555
DO - 10.1002/stem.1555
M3 - Article
C2 - 24115241
AN - SCOPUS:84894245083
VL - 32
SP - 730
EP - 740
JO - Stem Cells
JF - Stem Cells
SN - 1066-5099
IS - 3
ER -