Now showing items 1-17 of 17

    • Blocking phospholamban with VHH intrabodies enhances contractility and relaxation in heart failure 

      De Genst, Erwin; Foo, Kylie S; Xiao, Yao; Rohner, Eduarde; de Vries, Emma; Sohlmér, Jesper; Witman, Nevin; Hidalgo, Alejandro; Kolstad, Terje R S; Louch, William E; Pehrsson, Susanne; Park, Andrew; Ikeda, Yasuhiro; Li, Xidan; Mayr, Lorenz M; Wickson, Kate; Jennbacken, Karin; Hansson, Kenny; Fritsche-Danielson, Regina; Hunt, James; Chien, Kenneth R (Inst för cell- och molekylärbiologi / Dept of Cell and Molecular Biology, 2022-08-19)
      The dysregulated physical interaction between two intracellular membrane proteins, the sarco/endoplasmic reticulum Ca2+ ATPase and its reversible inhibitor phospholamban, induces heart failure by inhibiting calcium cycling. ...
    • Phospholamban antisense oligonucleotides improve cardiac function in murine cardiomyopathy 

      Beverborg, Niels Grote; Spater, Daniela; Knoll, Ralph; Hidalgo, Alejandro; Yeh, Steve T; Elbeck, Zaher; Sillje, Herman H W; Eijgenraam, Tim R; Siga, Humam; Zurek, Magdalena; Palmer, Malin; Pehrsson, Susanne; Albery, Tamsin; Bomer, Nils; Hoes, Martijn F; Boogerd, Cornelis J; Frisk, Michael; van Rooij, Eva; Damle, Sagar; Louch, William E; Wang, Qing-Dong; Fritsche-Danielson, Regina; Chien, Kenneth R; Hansson, Kenny M; Mullick, Adam E; de Boer, Rudolf A; van der Meer, Peter (Inst för cell- och molekylärbiologi / Dept of Cell and Molecular Biology, 2022-08-18)
      Heart failure (HF) is a major cause of morbidity and mortality worldwide, highlighting an urgent need for novel treatment options, despite recent improvements. Aberrant Ca2+ handling is a key feature of HF pathophysiology. ...
    • An mRNA assay system demonstrates proteasomal-specific degradation contributes to cardiomyopathic phospholamban null mutation 

      Rohner, Eduarde; Witman, Nevin; Sohlmér, Jesper; De Genst, Erwin; Louch, William E; Sahara, Makoto; Chien, Kenneth R (Inst för cell- och molekylärbiologi / Dept of Cell and Molecular Biology, 2022-08-17)
      Background: The human L39X phospholamban (PLN) cardiomyopathic mutant has previously been reported as a null mutation but the detailed molecular pathways that lead to the complete lack of detectable protein remain to be ...
    • Migratory and anti-fibrotic programmes define the regenerative potential of human cardiac progenitors 

      Poch, Christine M; Foo, Kylie S; De Angelis, Maria Teresa; Jennbacken, Karin; Santamaria, Gianluca; Bähr, Andrea; Wang, Qing-Dong; Reiter, Franziska; Hornaschewitz, Nadja; Zawada, Dorota; Bozoglu, Tarik; My, Ilaria; Meier, Anna; Dorn, Tatjana; Hege, Simon; Lehtinen, Miia L; Tsoi, Yat Long; Hovdal, Daniel; Hyllner, Johan; Schwarz, Sascha; Sudhop, Stefanie; Jurisch, Victoria; Sini, Marcella; Fellows, Mick D; Cummings, Matthew; Clarke, Jonathan; Baptista, Ricardo; Eroglu, Elif; Wolf, Eckhard; Klymiuk, Nikolai; Lu, Kun; Tomasi, Roland; Dendorfer, Andreas; Gaspari, Marco; Parrotta, Elvira; Cuda, Giovanni; Krane, Markus; Sinnecker, Daniel; Hoppmann, Petra; Kupatt, Christian; Fritsche-Danielson, Regina; Moretti, Alessandra; Chien, Kenneth R; Laugwitz, Karl-Ludwig (Inst för cell- och molekylärbiologi / Dept of Cell and Molecular Biology, 2022-08-02)
      Heart regeneration is an unmet clinical need, hampered by limited renewal of adult cardiomyocytes and fibrotic scarring. Pluripotent stem cell-based strategies are emerging, but unravelling cellular dynamics of host–graft ...
    • Human ISL1+ ventricular progenitors self-assemble into an in vivo functional heart patch and preserve cardiac function post infarction 

      Foo, Kylie S; Lehtinen, Miia L; Lian, Xiaojun; Xu, Jiejia; Keung, Wendy; Geng, Lin; Kolstad, Terje R S; Thams, Sebastian; Wong, Andy On-tik; Wong, Nicodemus; Bylund, Kristine; Zhou, Chikai; He, Xiaobing; Jin, Shao-Bo; Clarke, Jonathan; Lendahl, Urban; Li, Ronald A; Louch, William E; Chien, Kenneth R (Inst för cell- och molekylärbiologi / Dept of Cell and Molecular Biology, 2021-07-01)
      The generation of human pluripotent stem cell (hPSC)-derived ventricular progenitors and their assembly into a 3-dimensional in vivo functional ventricular heart patch has remained an elusive goal. Herein, we report the ...
    • A DNA-nanoassembly-based approach to map membrane protein nanoenvironments 

      Ambrosetti, Elena; Bernardinelli, Giulio; Hoffecker, Ian; Hartmanis, Leonard; Kiriako, Georges; de Marco, Ario; Sandberg, Rickard; Högberg, Björn; Teixeira, Ana I (Inst för medicinsk biokemi och biofysik / Dept of Medical Biochemistry and Biophysics, 2021-03-05)
      Most proteins at the plasma membrane are not uniformly distributed but localize to dynamic domains of nanoscale dimensions. To investigate their functional relevance, there is a need for methods that enable comprehensive ...
    • Trajectory mapping of human embryonic stem cell cardiogenesis reveals lineage branch points and an ISL1 progenitor-derived cardiac fibroblast lineage 

      Mononen, Mimmi; Leng, Chuen Yan; Xu, Jiejia; Chien, Kenneth R (Inst för cell- och molekylärbiologi / Dept of Cell and Molecular BiologyInst för medicin, Huddinge / Dept of Medicine, Huddinge, 2021-02-17)
      A family of multipotent heart progenitors plays a central role in the generation of diverse myogenic and nonmyogenic lineages in the heart. Cardiac progenitors in particular play a significant role in lineages involved in ...
    • Cardiac progenitors and paracrine mediators in cardiogenesis and heart regeneration 

      Witman, Nevin; Zhou, Chikai; Grote Beverborg, Niels; Sahara, Makoto; Chien, Kenneth R (Inst för cell- och molekylärbiologi / Dept of Cell and Molecular Biology, 2021-02-17)
      The mammalian hearts have the least regenerative capabilities among tissues and organs. As such, heart regeneration has been and continues to be the ultimate goal in the treatment against acquired and congenital heart ...
    • Population and single-cell analysis of human cardiogenesis reveals unique LGR5 ventricular progenitors in embryonic outflow tract 

      Sahara, Makoto; Santoro, Federica; Sohlmér, Jesper; Zhou, Chikai; Witman, Nevin; Leung, Chuen Yan; Mononen, Mimmi; Bylund, Kristine; Gruber, Peter; Chien, Kenneth R (Inst för cell- och molekylärbiologi / Dept of Cell and Molecular BiologyInst för medicin, Huddinge / Dept of Medicine, Huddinge, 2021-02-15)
      The morphogenetic process of mammalian cardiac development is complex and highly regulated spatiotemporally by multipotent cardiac stem/progenitor cells (CPCs). Mouse studies have been informative for understanding mammalian ...
    • Genome‐wide CRISPR screen identifies ZIC2 as an essential gene that controls the cell fate of early mesodermal precursors to human heart progenitors 

      Xu, Jiejia; Zhou, Chikai; Foo, Kylie S; Yang, Ran; Xiao, Yao; Bylund, Kristine; Sahara, Makoto; Chien, Kenneth R (Inst för cell- och molekylärbiologi / Dept of Cell and Molecular Biology, 2021-02-15)
      Cardiac progenitor formation is one of the earliest committed steps of human cardiogenesis and requires the cooperation of multiple gene sets governed by developmental signaling cascades. To determine the key regulators ...
    • X-chromosome upregulation is driven by increased burst frequency 

      Larsson , Anton J M; Coucoravas, Christos; Sandberg, Rickard; Reinius, Björn (Inst för medicinsk biokemi och biofysik / Dept of Medical Biochemistry and BiophysicsInst för cell- och molekylärbiologi / Dept of Cell and Molecular Biology, 2020-05-12)
      Ohno's hypothesis postulates that X-chromosome upregulation rectifies X-dose imbalance relative to autosomal genes, present in two active copies per cell. Here we dissected X-upregulation into kinetics of transcription, ...
    • Serum proteases potentiate BMP-induced cell cycle re-entry of dedifferentiating muscle cells during newt limb regeneration 

      Wagner, Ines; Wang, Heng; Weissert, Philipp; Straube, Werner; Shevchenko, Anna; Gentzel, Marc; Brito, Gonçalo M; Tazaki, Akira; Oliveira, Catarina; Sugiura, Takuji; Shevchenko, Andrej; Simon, András; Drechsel, David; Tanaka, Elly (Inst för cell- och molekylärbiologi / Dept of Cell and Molecular Biology, 2018-02-12)
      Limb amputation in the newt induces myofibers to dedifferentiate and re-enter the cell cycle to generate proliferative myogenic precursors in the regeneration blastema. Here we show that bone morphogenetic proteins (BMPs) ...
    • Skeletal muscle dedifferentiation during salamander limb regeneration 

      Wang, Heng; Simon, András (Inst för cell- och molekylärbiologi / Dept of Cell and Molecular Biology, 2018-01-24)
      Salamanders can regenerate entire limbs throughout their life. A critical step during limb regeneration is formation of a blastema, which gives rise to the new extremity. Salamander limb regeneration has historically been ...
    • High density of REC8 constrains sister chromatid axes and prevents illegitimate synaptonemal complex formation 

      Agostinho, Ana; Manneberg, Otto; van Schendel, Robin; Hernández-Hernández, Abrahan; Kouznetsova, Anna; Blom, Hans; Brismar, Hjalmar; Höög, Christer (Inst för cell- och molekylärbiologi / Dept of Cell and Molecular Biology, 2016-12-07)
      During meiosis, cohesin complexes mediate sister chromatid cohesion (SCC), synaptonemal complex (SC) assembly and synapsis. Here, using super-resolution microscopy, we imaged sister chromatid axes in mouse meiocytes that ...
    • TFAM forces mtDNA to make a U-turn 

      Hällberg, B Martin; Larsson, Nils-Göran (Inst för cell- och molekylärbiologi / Dept of Cell and Molecular Biology, 2014-08-04)
      The mammalian mitochondrial transcription factor A (TFAM) is encoded in the nucleus and imported into mitochondria, where it functions as an activator of mtDNA transcription and packages mtDNA into DNA-protein aggregates ...
    • Making proteins in the powerhouse 

      Hällberg, B Martin; Larsson, Nils-Göran (Inst för cell- och molekylärbiologi / Dept of Cell and Molecular Biology, 2014-08-04)
      Understanding regulation of mitochondrial DNA (mtDNA) expression is of considerable interest as mitochondrial dysfunction is important in human pathology and ageing. Similar to the situation in bacteria, there is no ...
    • Inhibition of proteasome deubiquitinating activity as a novel cancer therapy 

      D'Arcy, Pádraig; Brnjic, Slavica; Olofsson, Maria Hägg; Fryknäs, Mårten; Lindsten, Kristina; De Cesare, Michelandrea; Perego, Paola; Sadeghi, Behnam; Hassan, Moustapha; Larsson, Rolf; Linder, Stig (Inst för onkologi-patologi / Dept of Oncology-Pathology, 2013-04-22)
      Ubiquitin-tagged substrates are degraded by the 26S proteasome, which is a multisubunit complex comprising a proteolytic 20S core particle capped by 19S regulatory particles. The approval of bortezomib for the treatment ...