Extracellular matrix protein tenascin-C is required in the bone marrow microenvironment primed for hematopoietic regeneration

Ayako Nakamura-Ishizu, Yuji Okuno, Yoshiki Omatsu, Keisuke Okabe, Junko Morimoto, Toshimitsu Uede, Takashi Nagasawa, Toshio Suda, Yoshiaki Kubota

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

The BM microenvironment is required for the maintenance, proliferation, and mobilization of hematopoietic stem and progenitor cells (HSPCs), both during steady-state conditions and hematopoietic recovery after myeloablation. The ECM meshwork has long been recognized as a major anatomical component of the BM microenvironment; however, the molecular signatures and functions of the ECM to support HSPCs are poorly understood. Of the many ECM proteins, the expression of tenascin-C (TN-C) was found to be dramatically up-regulated during hematopoietic recovery after myeloablation. The TN-C gene was predominantly expressed in stromal cells and endothelial cells, known as BM niche cells, supporting the function of HSPCs. Mice lacking TN-C (TN-C -/-) mice showed normal steady-state hematopoiesis; however, they failed to reconstitute hematopoiesis after BM ablation and showed high lethality. The capacity to support transplanted wild-type hematopoietic cells to regenerate hematopoiesis was reduced in TN-C -/- recipient mice. In vitro culture on a TN-C substratum promoted the proliferation of HSPCs in an integrin α9-dependent manner and up-regulated the expression of the cyclins (cyclinD1 and cyclinE1) and down-regulated the expression of the cyclin-dependent kinase inhibitors (p57 Kip2, p21 Cip1, p16 Ink4a). These results identify TN-C as a critical component of the BM microenvironment that is required for hematopoietic regeneration.

Original languageEnglish
Pages (from-to)5429-5437
Number of pages9
JournalBlood
Volume119
Issue number23
DOIs
Publication statusPublished - 2012 Jun 7

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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