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2014-04-25 - Colloque/Présentation - poster - Anglais - 1 page(s)

De La Kethulle De Ryhove Laurence, Ansseau Eugénie , Geens Mieke, Coppée Frédérique , Sermon Karen, Lagneaux Laurence, Belayew Alexandra , "DUX4 expression during Osteogenic Differentiation in MSCs" in 20th ISCT Annual Meeting (International Society Cellular Therapy) 2014, Palais des Congrès, Paris, France, 2014

  • Codes CREF : Biologie moléculaire (DI3111)
  • Unités de recherche UMONS : Biochimie métabolique et moléculaire (M122)
  • Instituts UMONS : Institut des Sciences et Technologies de la Santé (Santé)

Abstract(s) :

(Anglais) Our group has identified the Double Homeobox 4 (DUX4)1 gene within repeated DNA elements in the 4q35 chromosome region linked to the FSHD muscular dystrophy. In healthy individuals, Dr. S. Tapscott’s group2 has detected a full length DUX4 mRNA (fl-DUX4) in induced pluripotent stem (iPS) cells and human testis, and a longer mRNA where the gene contains 4 additional exons and a more distal polyadenylation signal than in FSHD muscles. Our preliminary data suggested DUX4 was expressed at a very low level in MSC isolated from bone marrow (BM-MSC) and more abundant in Wharton jelly (Wj-MSC). We wanted to evaluate whether DUX4 expression changed during BM-MSC differentiation. We added an osteogenic differentiation medium to BM-MSCs cultures, collected cells after 0, 7, 14 and 21 days and performed an immunodetection on western blot. To confirm the differentiation process we stained calcium deposits in the cell culture dishes with alizarin red. We observed an increase of DUX4 expression after 14 and 21 days. We then investigated whether DUX4 was involved in the differentiation process. We transfected MSCs with antisense oligonucleotides (2’O Methyl phosphorothiate, DUX4-AO) targeting the DUX4 mRNA and previously shown to interfere with the protein expression3. The cells transfected with a DUX4-AO presented weaker alizarin red staining after switch to differentiation medium (Fig.1). In conclusion we show that DUX4 expression is increased upon MSC differentiation to osteoblasts. This observation is in contrast with the data published about iPS cells differentiation to embryoid bodies in which DUX4-fl expression disappeared2. However Dr. M. Kyba’s group has recently shown DUX4 implication in neurogenesis4. They transfected murine embryonic stem cells with a DUX4 inducible vector and observed after DUX4 induction that differentiated cells expressed neuronal expression markers. We hypothesize that DUX4 could generally be implicated in the mechanism of early differentiation.