RRC ID 17573
Author Nakamura-Ishizu A, Okuno Y, Omatsu Y, Okabe K, Morimoto J, Uede T, Nagasawa T, Suda T, Kubota Y.
Title Extracellular matrix protein tenascin-C is required in the bone marrow microenvironment primed for hematopoietic regeneration.
Journal Blood
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.
Volume 119(23)
Pages 5429-37
Published 2012-6-7
DOI 10.1182/blood-2011-11-393645
PII blood-2011-11-393645
PMID 22553313
PMC PMC3418770
MeSH Animals Bone Marrow / drug effects Bone Marrow / metabolism* Bone Marrow / radiation effects Bone Marrow Cells / cytology* Bone Marrow Cells / metabolism Bone Marrow Transplantation Cell Proliferation Endothelial Cells / cytology Endothelial Cells / metabolism Fluorouracil / administration & dosage Fluorouracil / adverse effects Gene Deletion Hematopoiesis* Hematopoietic Stem Cells / cytology* Hematopoietic Stem Cells / metabolism Integrin alpha Chains / genetics Mice Mice, Inbred C57BL RNA, Messenger / genetics Stromal Cells / cytology Stromal Cells / metabolism Tenascin / analysis Tenascin / genetics Tenascin / metabolism* Up-Regulation Whole-Body Irradiation
IF 16.601
Times Cited 33
Mice C57BL/6N-TgH(Tnc) (RBRC00169)