title: Brief Report: Alternative Splicing of Extra Domain A (EIIIA) of Fibronectin Plays a Tissue-Specific Role in Hematopoietic Homeostasis.
abstract: Fibronectin (FN) is a major extracellular matrix protein implicated in cell adhesion and differentiation in the bone marrow (BM) environment. Alternative splicing of FN gene results in the generation of protein variants containing an additional EIIIA domain that sustains cell proliferation or differentiation during physiological or pathological tissue remodeling. To date its expression and role in adult hematopoiesis has not been explored. In our research, we demonstrate that during physiological hematopoiesis a small fraction of BM derived FN contains the EIIIA domain and that mice constitutively including (EIIIA(+/+) ) or excluding (EIIIA(-/-) ) the EIIIA exon present comparable levels of hematopoietic stem cells, myeloid and lymphoid progenitors within BM. Moreover, only minor alterations were detected in blood parameters and in hematopoietic frequencies of BM granulocytes/monocytes and B cells. As opposed to other tissues, unique compensatory mechanisms, such as increased FN accumulation and variable expression of the EIIIA receptors, Toll like receptor-4 and alpha9 integrin subunit, characterized the BM of these mice. Our data demonstrate that FN is a fundamental component of the hematopoietic tissue and that the EIIIA exon may play a key role in modulating hematopiesis in conditions of BM stress or diseases. Stem Cells 2016;34:2263-2268.
authors.affiliation: Department of Molecular Medicine, University of Pavia, Pavia, Italy.|Laboratory of Biotechnology, IRCCS San Matteo Foundation, Pavia, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Malara
authors.affiliation: Department of Molecular Medicine, University of Pavia, Pavia, Italy.
authors.forename: Cristian
authors.initials: C
authors.lastname: Gruppi
authors.affiliation: Laboratory of Molecular Gastroenterology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Celesti
authors.affiliation: Immunohaematology and Transfusion Service, Apheresis and Cell Therapy Unit, IRCCS San Matteo Foundation, Pavia, Italy.
authors.forename: Bina
authors.initials: B
authors.lastname: Romano
authors.affiliation: Laboratory of Molecular Gastroenterology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Laghi
authors.affiliation: Department of Laboratory Diagnostics and Cell Therapy, National Cancer Center (IRCCS CRO), Aviano, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: De Marco
authors.affiliation: The International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.
authors.forename: Andrés F
authors.initials: AF
authors.lastname: Muro
authors.affiliation: Department of Molecular Medicine, University of Pavia, Pavia, Italy.|Laboratory of Biotechnology, IRCCS San Matteo Foundation, Pavia, Italy.|Department of Biomedical Engineering, Tufts University, Medford, MA, USA.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Balduini
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D005353:Fibronectins / Q000737:chemistry* / Q000235:genetics*; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006706:Homeostasis; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity; D000072417:Protein Domains
chemical_list: D005353:Fibronectins
keywords: Alternative splicing; Bone marrow; Fibronectin; Hematopoiesis