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

72 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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Tenascin
Extracellular Matrix Proteins
Hematopoietic Stem Cells
Protein C
Regeneration
Bone
Bone Marrow
Military electronic countermeasures
Hematopoiesis
Recovery
Endothelial cells
Ablation
Integrins
Stromal Cells
Phosphotransferases
Genes
Endothelial Cells
Maintenance

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Extracellular matrix protein tenascin-C is required in the bone marrow microenvironment primed for hematopoietic regeneration. / Nakamura-Ishizu, Ayako; Okuno, Yuji; Omatsu, Yoshiki; Okabe, Keisuke; Morimoto, Junko; Uede, Toshimitsu; Nagasawa, Takashi; Suda, Toshio; Kubota, Yoshiaki.

In: Blood, Vol. 119, No. 23, 07.06.2012, p. 5429-5437.

Research output: Contribution to journalArticle

Nakamura-Ishizu, Ayako ; Okuno, Yuji ; Omatsu, Yoshiki ; Okabe, Keisuke ; Morimoto, Junko ; Uede, Toshimitsu ; Nagasawa, Takashi ; Suda, Toshio ; Kubota, Yoshiaki. / Extracellular matrix protein tenascin-C is required in the bone marrow microenvironment primed for hematopoietic regeneration. In: Blood. 2012 ; Vol. 119, No. 23. pp. 5429-5437.
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