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

研究成果: Article

85 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)5429-5437
ページ数9
ジャーナルBlood
119
23
DOI
出版ステータスPublished - 2012 6 7

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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