Extracellular Matrix Protein Tenascin-C is Required in the Bone Marrow Microenvironment Primed for Hematopoietic Regeneration

Overview

Journal Blood

Publisher Elsevier

Specialty Hematology

Date 2012 May 4

PMID 22553313

Citations 69

Authors

Ayako Nakamura-Ishizu

Yuji Okuno

Yoshiki Omatsu

Keisuke Okabe

Junko Morimoto

Toshimitsu Uede

Takashi Nagasawa

Toshio Suda

Yoshiaki Kubota

Affiliations

Soon will be listed here.

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.

Citing Articles

Tenascin-C promotes bone regeneration via inflammatory macrophages.

Ren Q, Xing W, Jiang B, Feng H, Hu X, Suo J Cell Death Differ. 2025; .

PMID: 39794452 DOI: 10.1038/s41418-024-01429-9.

Tenascin-C from the tissue microenvironment promotes muscle stem cell self-renewal through Annexin A2.

Loreti M, Cecchini A, Kaufman C, Stamenkovic C, Renero A, Nicoletti C bioRxiv. 2024; .

PMID: 39554125 PMC: 11565721. DOI: 10.1101/2024.10.29.620732.

Emerging insights into epigenetics and hematopoietic stem cell trafficking in age-related hematological malignancies.

Xinyi Y, Vladimirovich R, Beeraka N, Satyavathi A, Kamble D, Nikolenko V Stem Cell Res Ther. 2024; 15(1):401.

PMID: 39506818 PMC: 11539620. DOI: 10.1186/s13287-024-04008-4.

The insertion/deletion polymorphism rs201494641 at influences blood CD34 cell levels by altering ZNF384 binding.

Cafaro C, Ali Z, Lamarca A, Di Bello D, Lozano L, Ekdahl L Haematologica. 2024; 109(9):3059-3062.

PMID: 38721738 PMC: 11367236. DOI: 10.3324/haematol.2024.285363.

Spatiotemporal dynamics exhibited by horizontal basal cells reveal a pro-neurogenic pathway during injury-induced olfactory epithelium regeneration.

Louie J, Barrios-Camacho C, Bromberg B, Hintschich C, Schwob J iScience. 2024; 27(5):109600.

PMID: 38650985 PMC: 11033173. DOI: 10.1016/j.isci.2024.109600.

References

Morikawa S, Mabuchi Y, Kubota Y, Nagai Y, Niibe K, Hiratsu E . Prospective identification, isolation, and systemic transplantation of multipotent mesenchymal stem cells in murine bone marrow. J Exp Med. 2009; 206(11):2483-96. PMC: 2768869. DOI: 10.1084/jem.20091046. View

Zuckerman K, Wicha M . Extracellular matrix production by the adherent cells of long-term murine bone marrow cultures. Blood. 1983; 61(3):540-7. View

Yokosaki Y, Monis H, Chen J, Sheppard D . Differential effects of the integrins alpha9beta1, alphavbeta3, and alphavbeta6 on cell proliferative responses to tenascin. Roles of the beta subunit extracellular and cytoplasmic domains. J Biol Chem. 1996; 271(39):24144-50. DOI: 10.1074/jbc.271.39.24144. View

Mendez-Ferrer S, Michurina T, Ferraro F, Mazloom A, MacArthur B, Lira S . Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature. 2010; 466(7308):829-34. PMC: 3146551. DOI: 10.1038/nature09262. View

Yokosaki Y, Palmer E, Prieto A, Crossin K, Bourdon M, Pytela R . The integrin alpha 9 beta 1 mediates cell attachment to a non-RGD site in the third fibronectin type III repeat of tenascin. J Biol Chem. 1994; 269(43):26691-6. View

Arai F, Hirao A, Ohmura M, Sato H, Matsuoka S, Takubo K . Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell. 2004; 118(2):149-61. DOI: 10.1016/j.cell.2004.07.004. View

Wirl G, Hermann M, Ekblom P, Fassler R . Mammary epithelial cell differentiation in vitro is regulated by an interplay of EGF action and tenascin-C downregulation. J Cell Sci. 1995; 108 ( Pt 6):2445-56. DOI: 10.1242/jcs.108.6.2445. View

Omatsu Y, Sugiyama T, Kohara H, Kondoh G, Fujii N, Kohno K . The essential functions of adipo-osteogenic progenitors as the hematopoietic stem and progenitor cell niche. Immunity. 2010; 33(3):387-99. DOI: 10.1016/j.immuni.2010.08.017. View

Kanayama M, Kurotaki D, Morimoto J, Asano T, Matsui Y, Nakayama Y . Alpha9 integrin and its ligands constitute critical joint microenvironments for development of autoimmune arthritis. J Immunol. 2009; 182(12):8015-25. DOI: 10.4049/jimmunol.0900725. View

10.

Moore K, Lemischka I . Stem cells and their niches. Science. 2006; 311(5769):1880-5. DOI: 10.1126/science.1110542. View

11.

Wilson A, Trumpp A . Bone-marrow haematopoietic-stem-cell niches. Nat Rev Immunol. 2006; 6(2):93-106. DOI: 10.1038/nri1779. View

12.

Calvi L, Adams G, Weibrecht K, Weber J, Olson D, Knight M . Osteoblastic cells regulate the haematopoietic stem cell niche. Nature. 2003; 425(6960):841-6. DOI: 10.1038/nature02040. View

13.

Andrews M, Czvitkovich S, Dassie E, Vogelaar C, Faissner A, Blits B . Alpha9 integrin promotes neurite outgrowth on tenascin-C and enhances sensory axon regeneration. J Neurosci. 2009; 29(17):5546-57. PMC: 6665849. DOI: 10.1523/JNEUROSCI.0759-09.2009. View

14.

Soini Y, Kamel D, Apaja-Sarkkinen M, Virtanen I, Lehto V . Tenascin immunoreactivity in normal and pathological bone marrow. J Clin Pathol. 1993; 46(3):218-21. PMC: 501173. DOI: 10.1136/jcp.46.3.218. View

15.

Adolfsson J, Borge O, Bryder D, Theilgaard-Monch K, Sitnicka E, Sasaki Y . Upregulation of Flt3 expression within the bone marrow Lin(-)Sca1(+)c-kit(+) stem cell compartment is accompanied by loss of self-renewal capacity. Immunity. 2001; 15(4):659-69. DOI: 10.1016/s1074-7613(01)00220-5. View

16.

Ohta M, Sakai T, Saga Y, Aizawa S, Saito M . Suppression of hematopoietic activity in tenascin-C-deficient mice. Blood. 1998; 91(11):4074-83. View

17.

Sato T, Laver J, Ogawa M . Reversible expression of CD34 by murine hematopoietic stem cells. Blood. 1999; 94(8):2548-54. View

18.

Grassinger J, Haylock D, Storan M, Haines G, Williams B, Whitty G . Thrombin-cleaved osteopontin regulates hemopoietic stem and progenitor cell functions through interactions with alpha9beta1 and alpha4beta1 integrins. Blood. 2009; 114(1):49-59. DOI: 10.1182/blood-2009-01-197988. View

19.

Matsuda A, Yoshiki A, Tagawa Y, Matsuda H, Kusakabe M . Corneal wound healing in tenascin knockout mouse. Invest Ophthalmol Vis Sci. 1999; 40(6):1071-80. View

20.

Kiel M, Yilmaz O, Iwashita T, Yilmaz O, Terhorst C, Morrison S . SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell. 2005; 121(7):1109-21. DOI: 10.1016/j.cell.2005.05.026. View