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Stem Cells. 2016 Aug;34(8):2263-8. doi: 10.1002/stem.2381. Epub 2016 May 4.

Brief Report: Alternative Splicing of Extra Domain A (EIIIA) of Fibronectin Plays a Tissue-Specific Role in Hematopoietic Homeostasis.

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Department of Molecular Medicine, University of Pavia, Pavia, Italy.
Laboratory of Biotechnology, IRCCS San Matteo Foundation, Pavia, Italy.
Laboratory of Molecular Gastroenterology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
Immunohaematology and Transfusion Service, Apheresis and Cell Therapy Unit, IRCCS San Matteo Foundation, Pavia, Italy.
Department of Laboratory Diagnostics and Cell Therapy, National Cancer Center (IRCCS CRO), Aviano, Italy.
The International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.
Department of Biomedical Engineering, Tufts University, Medford, MA, USA.


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.


Alternative splicing; Bone marrow; Fibronectin; Hematopoiesis

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