TY - GEN A1 - Olmer, Ruth A1 - Engels, Lena A1 - Usman, Abdulai A1 - Menke, Sandra A1 - Malik, Muhammad Nasir Hayat A1 - Pessler, Frank A1 - Göhring, Gudrun A1 - Bornhorst, Dorothee A1 - Bolten, Svenja A1 - Abdelilah-Seyfried, Salim A1 - Scheper, Thomas A1 - Kempf, Henning A1 - Zweigerdt, Robert A1 - Martin, Ulrich T1 - Differentiation of Human Pluripotent Stem Cells into Functional Endothelial Cells in Scalable Suspension Culture T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Endothelial cells (ECs) are involved in a variety of cellular responses. As multifunctional components of vascular structures, endothelial (progenitor) cells have been utilized in cellular therapies and are required as an important cellular component of engineered tissue constructs and in vitro disease models. Although primary ECs from different sources are readily isolated and expanded, cell quantity and quality in terms of functionality and karyotype stability is limited. ECs derived from human induced pluripotent stem cells (hiPSCs) represent an alternative and potentially superior cell source, but traditional culture approaches and 2D differentiation protocols hardly allow for production of large cell numbers. Aiming at the production of ECs, we have developed a robust approach for efficient endothelial differentiation of hiPSCs in scalable suspension culture. The established protocol results in relevant numbers of ECs for regenerative approaches and industrial applications that show in vitro proliferation capacity and a high degree of chromosomal stability. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1182 KW - virus infection KW - progenitor cells KW - in vitro KW - telomere dysfunction KW - cord blood KW - cardiomyogenic differentiation KW - angiogenesis KW - efficient KW - aberrations KW - expression Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-427095 SN - 1866-8372 IS - 5 ER - TY - JOUR A1 - Olmer, Ruth A1 - Engels, Lena A1 - Usman, Abdulai A1 - Menke, Sandra A1 - Malik, Muhammad Nasir Hayat A1 - Pessler, Frank A1 - Goehring, Gudrun A1 - Bornhorst, Dorothee A1 - Bolten, Svenja A1 - Abdelilah-Seyfried, Salim A1 - Scheper, Thomas A1 - Kempf, Henning A1 - Zweigerdt, Robert A1 - Martin, Ulrich T1 - Differentiation of Human Pluripotent Stem Cells into Functional Endothelial Cells in Scalable Suspension Culture JF - Stem Cell Reports N2 - Endothelial cells (ECs) are involved in a variety of cellular responses. As multifunctional components of vascular structures, endothelial (progenitor) cells have been utilized in cellular therapies and are required as an important cellular component of engineered tissue constructs and in vitro disease models. Although primary ECs from different sources are readily isolated and expanded, cell quantity and quality in terms of functionality and karyotype stability is limited. ECs derived from human induced pluripotent stem cells (hiPSCs) represent an alternative and potentially superior cell source, but traditional culture approaches and 2D differentiation protocols hardly allow for production of large cell numbers. Aiming at the production of ECs, we have developed a robust approach for efficient endothelial differentiation of hiPSCs in scalable suspension culture. The established protocol results in relevant numbers of ECs for regenerative approaches and industrial applications that show in vitro proliferation capacity and a high degree of chromosomal stability. KW - virus infection KW - progenitor cells KW - in vitro KW - telomere dysfunction KW - cord blood KW - cardiomyogenic differentiation KW - angiogenesis KW - efficient KW - aberrations KW - expression Y1 - 2017 U6 - https://doi.org/10.1016/j.stemcr.2018.03.017 SN - 2213-6711 VL - 10 IS - 5 PB - Springer CY - New York ER - TY - JOUR A1 - Lombardo, Verónica A. A1 - Heise, Melina A1 - Moghtadaei, Motahareh A1 - Bornhorst, Dorothee A1 - Männer, Jörg A1 - Abdelilah-Seyfried, Salim T1 - Morphogenetic control of zebrafish cardiac looping by Bmp signaling JF - Development : Company of Biologists N2 - Cardiac looping is an essential and highly conserved morphogenetic process that places the different regions of the developing vertebrate heart tube into proximity of their final topographical positions. High-resolution 4D live imaging of mosaically labelled cardiomyocytes reveals distinct cardiomyocyte behaviors that contribute to the deformation of the entire heart tube. Cardiomyocytes acquire a conical cell shape, which is most pronounced at the superior wall of the atrioventricular canal and contributes to S-shaped bending. Torsional deformation close to the outflow tract contributes to a torque-like winding of the entire heart tube between its two poles. Anisotropic growth of cardiomyocytes based on their positions reinforces S-shaping of the heart. During cardiac looping, bone morphogenetic protein pathway signaling is strongest at the future superior wall of the atrioventricular canal. Upon pharmacological or genetic inhibition of bone morphogenetic protein signaling, myocardial cells at the superior wall of the atrioventricular canal maintain cuboidal cell shapes and S-shaped bending is impaired. This description of cellular rearrangements and cardiac looping regulation may also be relevant for understanding the etiology of human congenital heart defects. KW - BMP KW - Wnt KW - Cardiac looping KW - Hemodynamics KW - Zebrafish Y1 - 2019 U6 - https://doi.org/10.1242/dev.180091 SN - 0950-1991 SN - 1477-9129 VL - 146 IS - 22 PB - The Company of Biologists Ltd CY - Cambridge ER - TY - JOUR A1 - Bornhorst, Dorothee A1 - Xia, Peng A1 - Nakajima, Hiroyuki A1 - Dingare, Chaitanya A1 - Herzog, Wiebke A1 - Lecaudey, Virginie A1 - Mochizuki, Naoki A1 - Heisenberg, Carl-Philipp A1 - Yelon, Deborah A1 - Abdelilah-Seyfried, Salim T1 - Biomechanical signaling within the developing zebrafish heart attunes endocardial growth to myocardial chamber dimensions JF - Nature Communications N2 - Intra-organ communication guides morphogenetic processes that are essential for an organ to carry out complex physiological functions. In the heart, the growth of the myocardium is tightly coupled to that of the endocardium, a specialized endothelial tissue that lines its interior. Several molecular pathways have been implicated in the communication between these tissues including secreted factors, components of the extracellular matrix, or proteins involved in cell-cell communication. Yet, it is unknown how the growth of the endocardium is coordinated with that of the myocardium. Here, we show that an increased expansion of the myocardial atrial chamber volume generates higher junctional forces within endocardial cells. This leads to biomechanical signaling involving VE-cadherin, triggering nuclear localization of the Hippo pathway transcriptional regulator Yap1 and endocardial proliferation. Our work suggests that the growth of the endocardium results from myocardial chamber volume expansion and ends when the tension on the tissue is relaxed. Y1 - 2019 U6 - https://doi.org/10.1038/s41467-019-12068-x SN - 2041-1723 VL - 10 PB - Nature Publ. Group CY - London ER - TY - GEN A1 - Bornhorst, Dorothee A1 - Abdelilah-Seyfried, Salim T1 - Strong as a Hippo’s Heart: Biomechanical Hippo Signaling During Zebrafish Cardiac Development T2 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - The heart is comprised of multiple tissues that contribute to its physiological functions. During development, the growth of myocardium and endocardium is coupled and morphogenetic processes within these separate tissue layers are integrated. Here, we discuss the roles of mechanosensitive Hippo signaling in growth and morphogenesis of the zebrafish heart. Hippo signaling is involved in defining numbers of cardiac progenitor cells derived from the secondary heart field, in restricting the growth of the epicardium, and in guiding trabeculation and outflow tract formation. Recent work also shows that myocardial chamber dimensions serve as a blueprint for Hippo signaling-dependent growth of the endocardium. Evidently, Hippo pathway components act at the crossroads of various signaling pathways involved in embryonic zebrafish heart development. Elucidating how biomechanical Hippo signaling guides heart morphogenesis has direct implications for our understanding of cardiac physiology and pathophysiology. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1236 KW - Hippo signaling KW - Yap1/Wwtr1 (Taz) KW - cardiac development KW - mechanobiology KW - endocardium KW - myocardium KW - zebrafish KW - intra-organ-communication Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-548731 SN - 1866-8372 SP - 1 EP - 10 PB - Universitätsverlag Potsdam CY - Potsdam ER - TY - JOUR A1 - Bornhorst, Dorothee A1 - Abdelilah-Seyfried, Salim T1 - Strong as a Hippo’s Heart: Biomechanical Hippo Signaling During Zebrafish Cardiac Development JF - Frontiers in Cell and Developmental Biology N2 - The heart is comprised of multiple tissues that contribute to its physiological functions. During development, the growth of myocardium and endocardium is coupled and morphogenetic processes within these separate tissue layers are integrated. Here, we discuss the roles of mechanosensitive Hippo signaling in growth and morphogenesis of the zebrafish heart. Hippo signaling is involved in defining numbers of cardiac progenitor cells derived from the secondary heart field, in restricting the growth of the epicardium, and in guiding trabeculation and outflow tract formation. Recent work also shows that myocardial chamber dimensions serve as a blueprint for Hippo signaling-dependent growth of the endocardium. Evidently, Hippo pathway components act at the crossroads of various signaling pathways involved in embryonic zebrafish heart development. Elucidating how biomechanical Hippo signaling guides heart morphogenesis has direct implications for our understanding of cardiac physiology and pathophysiology. KW - Hippo signaling KW - Yap1/Wwtr1 (Taz) KW - cardiac development KW - mechanobiology KW - endocardium KW - myocardium KW - zebrafish KW - intra-organ-communication Y1 - 2021 U6 - https://doi.org/10.3389/fcell.2021.731101 SN - 2296-634X VL - 9 SP - 1 EP - 10 PB - Frontiers Media CY - Lausanne, Schweiz ER -