Article
Cell Biology
Maria Cruz-Santos, Lucia Fernandez Cardo, Meng Li
Summary: GABAergic interneurons play a crucial role in controlling brain circuitry and network activity. Dysfunction of cortical interneurons, especially those derived from the medial ganglionic eminence, is associated with neurological disorders. Pluripotent stem cell-derived interneurons provide a valuable tool for studying the causes of neuropsychiatric disorders and have potential applications in cell therapy for neurological conditions like epilepsy.
Article
Multidisciplinary Sciences
Ryo Fujita, Seiya Mizuno, Taketaro Sadahiro, Takuto Hayashi, Takehito Sugasawa, Fumihiro Sugiyama, Yusuke Ono, Satoru Takahashi, Masaki Ieda
Summary: Researchers have developed a MyoD knock-in (MyoD-KI) mouse model that allows for monitoring the dynamic changes of MyoD protein in muscle stem cells (MuSCs). This model provides a valuable tool for studying the fate determination and heterogeneity of MuSCs, as well as for drug screening in stem cell therapy.
Article
Cell & Tissue Engineering
Teruyoshi Yamashita, Daisuke Kamiya, Nami Kawaraichi, Harufu Toyokawa, Teppei Akaboshi, Makoto Ikeya, Yayoi Toyooka
Summary: SOX10 is a definitive molecular marker of neural crest cells (NCCs) and an essential transcription factor for NCC differentiation in vertebrate embryogenesis. A human SOX10 knock-in reporter iPSC line was established using CRISPR/Cas9, allowing the monitoring of SOX10 expression as tdTomato fluorescence and providing a useful tool for modeling the differentiation process of human NCCs in vitro.
STEM CELL RESEARCH
(2022)
Article
Multidisciplinary Sciences
Agathe Lermant, Gwenaelle Rabussier, Henriette L. Lanz, Lindsay Davidson, Iain M. Porter, Colin E. Murdoch
Summary: This study successfully implemented hiPSC-derived trophoblasts into a multi-well microfluidic device, creating a physiologically relevant and scalable placental barrier model.
Article
Biochemical Research Methods
Elke Gabriel, Walid Albanna, Giovanni Pasquini, Anand Ramani, Natasa Josipovic, Aruljothi Mariappan, Maria Giovanna Riparbelli, Giuliano Callaini, Celeste M. M. Karch, Olivier Goureau, Argyris Papantonis, Volker Busskamp, Toni Schneider, Jay Gopalakrishnan
Summary: Induced pluripotent stem cell-derived brain organoids, known as OVB organoids, can deconstruct the developmental complexities of the human brain and help study interorgan interactions between optic vesicles and the brain. This protocol enables the generation of functional integrated bilateral optic vesicles and can be used to model early eye patterning defects.
Article
Cell & Tissue Engineering
Madison B. Wilken, Jean Ann Maguire, Alyssa Gagne, Catherine Osorio-Quintero, Elisa A. Waxman, Stella T. Chou, Paul Gadue, Deborah L. French, Christopher S. Thom
Summary: The CHOPWT17_TPM1KOc28 iPSC line was generated for investigating the roles of Tropomyosin 1 (TPM1) in primary human cell development. It was reprogrammed from a previously published wild type control iPSC line.
STEM CELL RESEARCH
(2023)
Article
Cell & Tissue Engineering
Johanna Siehler, Anna Karolina Bloechinger, Melis Akguen, Xianming Wang, Alireza Shahryari, Arie Geerlof, Heiko Lickert, Ingo Burtscher
Summary: This study presents a human iPSC line with mCherry labeled C-peptide generated by CRISPR/Cas9 technology, demonstrating efficient differentiation into pancreatic beta-like cells with red fluorescent C-peptide-mCherry fusion protein localization in insulin-containing granules. The HMGUi001-A-8 line serves as a valuable resource for purifying derived beta-like cells and real-time tracking of insulin-containing granules.
STEM CELL RESEARCH
(2021)
Article
Cell Biology
Parivash Nouri, Anja Zimmer, Stefanie Brueggemann, Robin Friedrich, Ralf Kuehn, Nilima Prakash
Summary: Advances in regenerative stem cell research have allowed for the generation of tissue-specific cells in vitro, which is important for transplantation, drug screening, and understanding the mechanisms of diseases. However, the heterogeneity of these cultures poses a challenge, as the cells of interest usually represent only a small fraction of all cells. In this study, the researchers used CRISPR-Cas9 technology to introduce a red fluorescent marker into human induced pluripotent stem cells, allowing for direct identification and isolation of neural stem/progenitor cells.
Article
Cell & Tissue Engineering
Wei Shan, Xiaoling Yang, Qian Ren, Qun Wang
Summary: The SCN1A gene encodes the Nav1.1 alpha subunit of voltage-gated Na+ channels, and variants in this gene are associated with a wide range of epilepsy syndromes. A human iPSC line with SCN1A knockout was successfully generated using CRISPR/Cas9, showing normal characteristics and differentiation potential.
STEM CELL RESEARCH
(2021)
Article
Cell & Tissue Engineering
Jian Fu, Lixiang Jiang, Baorong Yu, Yuqing Liu, Rui Wei, Yang Hu, Wan-In Ho, Bo Yang, Meng Chu, Hung-Fat Tse, Jiayin Yang
Summary: ASGR1 is a liver-specific surface marker used to purify human pluripotent stem cell-derived hepatocytes. The stop codon of ASGR1 was replaced with a fluorescent reporter protein mCherry via CRISPR/Cas9-mediated homologous recombination, resulting in the generation of CIBi010-A. CIBi010-A allows the monitoring of ASGR1 expression during hepatic differentiation and optimization of hepatic differentiation procedures.
STEM CELL RESEARCH
(2022)
Article
Multidisciplinary Sciences
Darcy T. Ahern, Prakhar Bansal, Maria K. Armillei, Isaac V. Faustino, Yuvabharath Kondaveeti, Heather R. Glatt-Deeley, Erin C. Banda, Stefan F. Pinter
Summary: This study investigates the impact of monosomy X on syncytiotrophoblast development in humans using X-monosomic human induced pluripotent stem cells (hiPSCs). The results suggest that monosomy X may alter the levels of placental genes and secretion of placental growth factor (PlGF) and human chorionic gonadotropin (hCG). The findings also demonstrate that the corresponding gene coexpression network modules are preserved in chorionic villi and term placenta.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Ingo Burtscher, Marta Tarquis-Medina, Ciro Salinno, Silvia Schirge, Julia Beckenbauer, Mostafa Bakhti, Heiko Lickert
Summary: Nkx6-1 is a key transcription factor in the regulation of motor neuron development, neuron specification, and pancreatic endocrine and beta-cell differentiation. The Nkx6-1-VF reporter protein accurately marks and tracks specific cell types, providing a unique tool for studying gene expression patterns during organ development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell & Tissue Engineering
Min Zhou, Qi Xing, Di Zhang, Cong Zhang, Yanqi Zhang, Jingyuan Zhang, Yongli Shan
Summary: By using CRISPR/Cas9 technology to insert the Akaluc gene at the AAVS1 locus, a clonal human embryonic stem stable cell line called AkalucHES was generated, which efficiently expresses Akaluc and can be easily traced in vivo, maintaining normal karyotype and capable of differentiating toward three germ layers.
STEM CELL RESEARCH
(2021)
Article
Cell & Tissue Engineering
Liliya Nazlamova, Emma-Jane Cassidy, Jane C. Sowden, Andrew Lotery, Jorn Lakowski
Summary: A fluorescent reporter cell line for human cone photoreceptors was generated using CRISPR/Cas9 genome editing, allowing for tracking and analysis of cone cell development. The reporter cell line accurately labels cone cells and reveals migratory activity during in vitro differentiation.
Article
Cell & Tissue Engineering
Seongyea Jo, Ji-Woo Kim, Haneul Noh, Hyemin Kim, Jong-Hoon Kim, Han-Jin Park
Summary: PDGFRB encodes PDGFR-beta, a cell surface receptor for platelet-derived growth factors. It plays important roles in the development of vascular and nervous systems, as well as actin cytoskeleton rearrangement. In liver diseases, particularly liver fibrosis, PDGFR-beta is essential. The generated iPSC line, KITi001-A-1, provides a useful tool for studying PDGFR-beta-expressing cells and screening liver fibrosis-inducing compounds.
STEM CELL RESEARCH
(2023)
Article
Hematology
Mania Ackermann, Kathrin Haake, Henning Kempf, Paul Kaschutnig, Anna-Carina Weiss, Ariane H. H. Nguyen, Markus Abeln, Sylvia Merkert, Mark Phillip Kuhnel, Dorothee Hartmann, Danny Jonigk, Thomas Thum, Andreas Kispert, Michael D. Milsom, Nico Lachmann
Summary: Embryonic hematopoietic development was successfully simulated using a 3D cell culture system, revealing the crucial role of interleukin 3 (IL-3) in the transition of hemato-endothelial progenitors to hematopoietic cells.
Article
Cell & Tissue Engineering
S. Merkert, M-C Jaboreck, L. Engels, M. N. H. Malik, G. Goehring, F. Pessler, U. Martin, R. Olmer
Summary: ISG15 is a highly upregulated protein in response to viral infection, and its deficiency can lead to type I interferonopathy while enhancing antiviral protection. Generating ISG15 knockout clones from human iPSCs provides valuable cell resources for studying ISG15 deficiency mechanisms and gaining deeper insights into its biological function.
STEM CELL RESEARCH
(2021)
Article
Biotechnology & Applied Microbiology
Lika Drakhlis, Santoshi Biswanath, Clara-Milena Farr, Victoria Lupanow, Jana Teske, Katharina Ritzenhoff, Annika Franke, Felix Manstein, Emiliano Bolesani, Henning Kempf, Simone Liebscher, Katja Schenke-Layland, Jan Hegermann, Lena Nolte, Heiko Meyer, Jeanne de la Roche, Stefan Thiemann, Christian Wahl-Schott, Ulrich Martin, Robert Zweigerdt
Summary: This study successfully generated three-dimensional heart-forming organoids that closely resemble early native heart anlagen, containing myocardial layer, endocardial-like cells, septum-transversum-like anlagen, and distinct anterior versus posterior foregut endoderm tissues. These organoids were used to study genetic defects in vitro and demonstrated a phenotype similar to cardiac malformations seen in transgenic mice with the knockout of NKX2.5 gene.
NATURE BIOTECHNOLOGY
(2021)
Article
Biochemical Research Methods
Anais Sahabian, Julia Dahlmann, Ulrich Martin, Ruth Olmer
Summary: The protocol described a detailed method for large-scale production of definitive endoderm (DE) cells from human pluripotent stem cells (hPSCs) with high purity. By using chemically defined and xeno-free media, a significant number of DE cells can be efficiently generated within a short period of time for downstream differentiation and research purposes.
Article
Cell & Tissue Engineering
Felix Manstein, Kevin Ullmann, Christina Kropp, Caroline Halloin, Wiebke Triebert, Annika Franke, Clara-Milena Farr, Anais Sahabian, Alexandra Haase, Yannik Breitkreuz, Michael Peitz, Oliver Brustle, Stefan Kalies, Ulrich Martin, Ruth Olmer, Robert Zweigerdt
Summary: By combining STBR technology with in silico process modeling, challenges in hPSC production were overcome, leading to a rapid 70-fold increase in cell expansion and maintenance of cell quality stability.
STEM CELLS TRANSLATIONAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Silvia Benito-Kwiecinski, Stefano L. Giandomenico, Magdalena Sutcliffe, Erlend S. Riis, Paula Freire-Pritchett, Iva Kelava, Stephanie Wunderlich, Ulrich Martin, Gregory A. Wray, Kate McDole, Madeline A. Lancaster
Summary: Research shows that neuroepithelial cell shape in apes is a protracted process, while human brain organoids are larger due to a delay in this transition. RNA sequencing reveals differences in expression dynamics of cell morphogenesis factors, including ZEB2.
Article
Cell & Tissue Engineering
Maria Elena Ricci Signorini, Monika Szepes, Anna Melchert, Mine Bakar, Sylvia Merkert, Alexandra Haase, Gudrun Gohring, Ulrich Martin, Ina Gruh
Summary: Calcium plays a crucial role in cardiomyocytes, translating electrical signals into contraction forces. A non-invasive fluorescence imaging technique allows for the monitoring of calcium changes in human induced pluripotent stem cell-derived cardiomyocytes, providing insights into cardiac electrophysiology in vitro and in vivo. Genetically encoded calcium indicators have been successfully introduced into a well-established hiPSC line, enabling the monitoring of calcium handling in highly pure populations of hiPSC-CMs.
STEM CELL RESEARCH
(2022)
Article
Medicine, Research & Experimental
Stephanie Wunderlich, Alexandra Haase, Sylvia Merkert, Kirsten Jahn, Maximillian Deest, Helge Frieling, Silke Glage, Wilhelm Korte, Andreas Martens, Andreas Kirschning, Andre Zeug, Evgeni Ponimaskin, Gudrun Goehring, Mania Ackermann, Nico Lachmann, Thomas Moritz, Robert Zweigerdt, Ulrich Martin
Summary: Drug-inducible suicide systems can help reduce the risk of drug-resistant subclones in hiPSC therapies, but rare drug-resistant subclones can still appear in monoallelic iCASP9 hiPSCs both in vitro and in vivo.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2022)
Article
Oncology
Syed Fakhar-ul-Hassnain Waqas, Aaqib Sohail, Ariane Hai Ha Nguyen, Abdulai Usman, Tobias Ludwig, Andre Wegner, Muhammad Nasir Hayat Malik, Sven Schuchardt, Robert Geffers, Moritz Winterhoff, Sylvia Merkert, Ulrich Martin, Ruth Olmer, Nico Lachmann, Frank Pessler
Summary: This study developed induced pluripotent stem cell-derived macrophages and endothelial cells as a model to study the cellular phenotype of ISG15 deficiency and identify novel treatments. The researchers found that ISG15 deficiency resulted in a multifaceted pathological phenotype, including increased inflammation, propensity for cell death, and oxidative stress. Treatment with itaconate, dimethyl-itaconate, 4-octyl-itaconate, and the JAK1/2 inhibitor ruxolitinib improved cellular function and gene expression, suggesting their potential as therapeutics for this rare disorder.
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
Article
Cell & Tissue Engineering
Mark-Christian Jaboreck, Jonathan Lukas Luehmann, Mia Mielenz, Frauke Stanke, Gudrun Goehring, Ulrich Martin, Ruth Olmer, Sylvia Merkert
Summary: In this study, knockout cell lines lacking the TMEM16A gene were generated using CRISPR/Cas9 technology in both healthy human induced pluripotent stem cells (iPSCs) and cystic fibrosis patient iPSCs. These cell lines can provide insights into the role of TMEM16A in mucus secretion and production, as well as evaluating its therapeutic potential.
STEM CELL RESEARCH
(2022)
Article
Cell & Tissue Engineering
Sylvia Merkert, Alexandra Haase, Julia Dahlmann, Gudrun Goehring, Fakhar H. Waqas, Frank Pessler, Ulrich Martin, Ruth Olmer
Summary: The nuclear factor erythroid 2-related factor 2 (NRF2) plays a role in regulating antioxidative and anti-inflammatory proteins. By using CRISPR/Cas9 editing, NRF2 was eliminated in the human iPS cell line MHHi001-A, resulting in two NRF2 knockout iPSC clones MHHi001-A-6 and MHHi001-A-7. These cells can be differentiated into epithelial or endothelial cells to investigate the antiviral effects of molecules activating the NRF2 signaling pathway.
STEM CELL RESEARCH
(2023)
Article
Cell Biology
Laura von Schledorn, David Puertollano Martin, Nicole Cleve, Janina Zoellner, Doris Roth, Ben Ole Staar, Jan Hegermann, Felix C. Ringshausen, Janna Nawroth, Ulrich Martin, Ruth Olmer
Summary: Primary ciliary dyskinesia (PCD) is a rare genetic disorder that affects the function of motile cilia in the respiratory tract, leading to chronic inflammation and lung damage. Current treatment options for PCD are only symptomatic, highlighting the need for curative therapies. In this study, researchers developed an in vitro model using human induced pluripotent stem cells (hiPSC) to recapitulate the diseased phenotype of PCD at the molecular, structural, and functional levels.
Article
Cell Biology
Ian O. Shum, Sylvia Merkert, Svitlana Malysheva, Kirsten Jahn, Nico Lachmann, Murielle Verboom, Helge Frieling, Michael Hallensleben, Ulrich Martin
Summary: Abnormalities during trophoblast development can lead to pregnancy-related complications, but the underlying mechanisms are established during the first trimester. Human pluripotent stem cell (hPSC) technology provides a renewable source of cells for studying these diseases. By optimizing the treatment protocol, we were able to generate trophoblast cells enriched for HLA-G(pos) EVT-like cells, which will aid in understanding placenta-related disorders and investigation of immune tolerance towards the fetus.
Article
Medicine, Research & Experimental
Muhammad Nasir Hayat Malik, Syed Fakhar-ul-Hassnain Waqas, Jana Zeitvogel, Jingyuan Cheng, Robert Geffers, Zeinab Abu-Elbaha Gouda, Ahmed Mahrous Elsaman, Ahmed R. Radwan, Matthias Schefzyk, Peter Braubach, Bernd Auber, Ruth Olmer, Mathias Musken, Lennart M. Roesner, Gisa Gerold, Sven Schuchardt, Sylvia Merkert, Ulrich Martin, Felix Meissner, Thomas Werfel, Frank Pessler
Summary: Ulcerating skin lesions are manifestations of human ISG15 deficiency. Chronic inflammation may not be the sole cause. Two siblings with ISG15 gene mutation were found to have recurrent skin ulcers that healed with scar formation after corticosteroid treatment. ISG15-deficient cells were found to impact cell migration and maintenance of cellular and tissue integrity.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
