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

Alessandro Malara, Cristian Gruppi, Giuseppe Celesti, Bina Romano, Luigi Andrea Giuseppe Laghi, Luigi De Marco, Andrés F. Muro, A. Balduini

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)2263-2268
Number of pages6
JournalStem Cells
Volume34
Issue number8
DOIs
Publication statusPublished - Aug 1 2016

Keywords

  • Alternative splicing
  • Bone marrow
  • Fibronectin
  • Hematopoiesis

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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