Hereditary Cerebral Hemorrhage with Amyloidosis-Dutch type (HCHWA-D) is an autosomal dominant hereditary disease caused by a point mutation in exon 17 of the APP gene. We generated human induced... Show moreHereditary Cerebral Hemorrhage with Amyloidosis-Dutch type (HCHWA-D) is an autosomal dominant hereditary disease caused by a point mutation in exon 17 of the APP gene. We generated human induced pluripotent stem cells (hiPSCs) from a symptomatic HCHWA-D patient by using non-integrating Sendai virus (SeV). The newly generated hiPSCs express all pluripotency markers, have a normal karyotype, carry the Dutch mutation, can differentiate in the three germ layers in vitro and are SeV free. Show less
Kosmidis, G.; Veerman, C.C.; Casini, S.; Verkerk, A.O.; Pas, S. van de; Bellin, M.; ... ; Bezzina, C.R. 2016
Endothelial cells (EC) translate biomechanical forces into functional and phenotypic responses that play important roles in cardiac development. Specifically, EC in areas of high shear stress, i.e.... Show moreEndothelial cells (EC) translate biomechanical forces into functional and phenotypic responses that play important roles in cardiac development. Specifically, EC in areas of high shear stress, i.e., in the cardiac outflow tract and atrioventricular canal, are characterized by high expression of Kruppel-like factor 2 (Klf2) and by transforming growth factor-beta (Tgf beta)-driven endothelial-to-mesenchymal transition. Extraembryonic venous obstruction (venous clip model) results in congenital heart malformations, and venous clip-induced alterations in shear stress-related gene expression are suggestive for an increase in cardiac shear stress. Here, we study the effects of shear stress on Klf2 expression and Tgf beta-associated signaling in embryonic EC in vivo using the venous clip model and in vitro by subjecting cultured EC to fluid flow. Cellular responses were assessed by analysis of Klf2, Tgf beta ligands, and their downstream signaling targets. Results show that, in embryonic EC, shear stress activates Tgf beta/Alk5 signaling and that induction of Klf2 is an Alk5 dependent process. Developmental Dynamics 240: 1670-1680, 2011. (C) 2011 Wiley-Liss, Inc. Show less
Egorova, A.D.; Heiden, K. van der; Pas, S. van de; Vennemann, P.; Poelma, C.; DeRuiter, M.C.; ... ; Hierck, B.P. 2011
