Translin/TRAX deficiency affects mesenchymal differentiation programs and induces bone marrow failure

Reiko Ishida, Katsunori Aoki, Kazuhiko Nakahara, Yuko Fukuda, Momoko Ohori, Yumi Saito, Kimihiko Kano, Junichiro Matsuda, Shigetaka Asano, Richard T. Maziarz, Masataka Kasai

Research output: Chapter in Book/Report/Conference proceedingChapter

3 Scopus citations

Abstract

The decision regarding self-renewal versus differentiation of hematopoietic stem cells (HSCs) is a crucial issue in bone marrow hematopoiesis. We have generated mice homozygous for an inactivating mutation of the whole Translin gene (Translin-/-) and investigated their hematopoietic status during early and later in life. Here we show that Translin deficiency affects mesenchymal differentiation and results in perturbation of self-renewal HSCs. Young Translin-/- mice, especially around 3 weeks of age, displayed markedly reduced lymphocyte counts in the peripheral blood, attributable to developmental arrest of B-lymphocytes in the earliest progenitor stage. With aging, progressive bone marrow failure was displayed, with developmental arrest of myeloid cells and B lymphocytes in a stroma-dependent manner, and eventually ectopic osteogenesis, vasculogenesis and adipogenesis resulted. Despite apparent hematopoietic aplasia, however, the frequency of HSCs in the bone marrow of mutant mice was remarkably increased. Furthermore, knockdown of Translin and its binding partner protein, TRAX, up-regulated genes associated with mesenchymal differentiation in a mesenchymal stem cell line. Taken together, these findings suggest that the Translin and TRAX complex influences both self-renewal and multilineage differentiation of HSCs by targeting mesenchymal stem/progenitor cells.

Original languageEnglish (US)
Title of host publicationStem Cells and Human Diseases
PublisherSpringer Netherlands
Pages467-484
Number of pages18
Volume9789400728011
ISBN (Electronic)9789400728011
ISBN (Print)940072800X, 9789400728004
DOIs
StatePublished - Apr 1 2012

Keywords

  • Bone marrow failure
  • HSCs
  • MSCs
  • TRAX
  • Translin

ASJC Scopus subject areas

  • Medicine(all)

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