CCAAT/enhancer-binding protein β expressed by bone marrow mesenchymal stromal cells regulates early B-cell lymphopoiesis

Satoshi Yoshioka, Yasuo Miura, Hisayuki Yao, Sakiko Satake, Yoshihiro Hayashi, Akihiro Tamura, Terutoshi Hishita, Tatsuo Ichinohe, Hideyo Hirai, Akifumi Takaor-Kondo, Taira Maekawa

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13 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)730-740
Number of pages11
JournalStem Cells
Volume32
Issue number3
DOIs
Publication statusPublished - 03-2014

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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    Yoshioka, S., Miura, Y., Yao, H., Satake, S., Hayashi, Y., Tamura, A., Hishita, T., Ichinohe, T., Hirai, H., Takaor-Kondo, A., & Maekawa, T. (2014). CCAAT/enhancer-binding protein β expressed by bone marrow mesenchymal stromal cells regulates early B-cell lymphopoiesis. Stem Cells, 32(3), 730-740. https://doi.org/10.1002/stem.1555