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Articles by Lorenz Studer
Induced pluripotent stem cells from discovery to translation
Abstract Two decades after the introduction of induced pluripotent stem cell (iPSC) technology, the field has evolved from a seminal biological discovery into a transformative clinical platform.
Genome-wide CRISPR screen identifies neddylation as a regulator of neuronal aging and AD neurodegeneration
Main text (Cell Stem Cell 31, 1162–1174.e1–e9; August 1, 2024) Our original manuscript erroneously listed the concentration of SB431542 as 10 mM instead of 10 μM in the dopamine neuron differentiation section of the Method details section. We apologize for this error, which has been corrected in the original version. The corrected manuscript also includes additional changes to comply with the open access policy requirements of the funder (Aligning Science Across Parkinson’s disease).
Forebrain assembloids support the development of fast-spiking human PVALB+ cortical interneurons and uncover schizophrenia-associated defects
Keywords human PSC parvalbumin interneuron schizophrenia human disease modeling organoid assembloid Introduction Schizophrenia is a debilitating disorder associated with a diverse group of positive, negative, and cognitive symptoms.
Telmisartan is neuroprotective in a hiPSC-derived spinal microtissue model for C9orf72 ALS via inhibition of neuroinflammation
Keywords neuroinflammation amyotrophic lateral sclerosis C9orf72 motor neurons astrocytes microglia triculture 3D microtissue drug screen sartans Introduction Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron (MN) degeneration in the brain and spinal cord, leading to progressive paralysis and death within 3–5 years (Lall and Baloh, 2017).
Leveraging CRISPR activation for rapid assessment of gene editing products in human pluripotent stem cells
Keywords human pluripotent stem cells CRISPR-mediated transcriptional activation silent gene editing knockins dTAG system knockouts reporter lines Introduction CRISPR-Cas9 has been widely used for various gene editing applications in human pluripotent stem cells (hPSCs), targeting both expressed genes and silent genes in hPSCs (Ben Jehuda et al., 2018; Hendriks et al., 2016).
Three-dimensional regulatory hubs support oncogenic programs in glioblastoma
Keywords glioblastoma 3D chromatin organization enhancer-promoter interactions enhancer hubs clonogenicity oncogenic program structural variants HiChIP single-cell RNA-seq CRISPRi regulatory hubs Get full text access Log in, subscribe or purchase for full access. References 1. Brennan, C.W. ∙ Verhaak, R.G.W. ∙ McKenna, A. ... The somatic genomic landscape of glioblastoma Cell. 2013; 155:462-477 2. Stupp, R. ∙ Mason, W.P. ∙ van den Bent, M.J. ...
MorPhiC Consortium: towards functional characterization of all human genes - Nature
Abstract Recent advances in functional genomics and human cellular models have substantially enhanced our understanding of the structure and regulation of the human genome. However, our grasp of the molecular functions of human genes remains incomplete and biased towards specific gene classes.
A framework for neural organoids, assembloids and transplantation studies - Nature
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Abstract As the field of neural organoids and assembloids rapidly expands, there is an emergent need for guidance and advice on designing, conducting and reporting experiments to increase the reproducibility and utility of these models.
By Paola Arlotta, Helen S. Bateup, J. Gray Camp, Silvia Cappello, Fred Gage, Jürgen A. Knoblich, Arnold R. Kriegstein, Madeline A. Lancaster, Guo-li Ming, Hideyuki Okano, Malin Parmar, In-Hyun Park, Orly Reiner, Hongjun Song, Lorenz Studer, Jun C. Takahashi, Giuseppe Testa, Barbara Treutlein, Flora M. Vaccarino
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Nature
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Suppression of ferroptosis by vitamin A or radical-trapping antioxidants is essential for neuronal development - Nature Communications
Abstract The development of functional neurons is a complex orchestration of multiple signaling pathways controlling cell proliferation and differentiation. Because the balance of antioxidants is important for neuronal survival and development, we hypothesized that ferroptosis must be suppressed to gain neurons.
Human TMEFF1 is a restriction factor for herpes simplex virus in the brain
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Abstract Most cases of herpes simplex virus 1 (HSV-1) encephalitis (HSE) remain unexplained1,2. Here, we report on two unrelated people who had HSE as children and are homozygous for rare deleterious variants of TMEFF1, which encodes a cell membrane protein that is preferentially expressed by brain cortical neurons. TMEFF1 interacts with the cell-surface HSV-1 receptor NECTIN-1, impairing HSV-1 glycoprotein D- and NECTIN-1-mediated fusion of the virus and the cell membrane, blocking viral entry.
By Yi-Hao Chan, zhiyong Liu, Paul Bastard, Noopur V. Khobrekar, Yasuhiro Yamazaki, Qing Fan, Daniela Matuozzo, Oliver Harschnitz, Koji Nakajima, Ahmad Yatim, Darawan Rinchai, Jie Chen, Peng Zhang, Gabriele Ciceri, Jia Chen, Kerry Dobbs, Serkan Belkaya, Danyel Lee, Adrian Gervais, Kürşad Aydın, Ayşe Nur Kartal, Shuxiang Zhao, Eduardo Garcia Reino, Yoon Seung Lee, Yoann Seeleuthner, Matthieu Chaldebas, Rasheed Bailey, Lazaro Lorenzo, Soraya Boucherit, Nico Marr, Trine H. Mogensen, Melodie Aubart, Aurélie Cobat, Olivier Dulac, Melike Emiroglu, Søren R. Paludan, Laurent Abel, Luigi D. Notarangelo, Richard Longnecker, Greg Smith Verified, Lorenz Studer, Jean-Laurent Casanova Verified, Shen-Ying Zhang, Kennen M. Hutchison, Nacim Kerrouche, Mary L. Hasek, Catherine Vanhulle, Flore Rozenberg
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Nature
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Integrating population genetics, stem cell biology and cellular genomics to study complex human diseases - Nature Genetics
Abstract Human pluripotent stem (hPS) cells can, in theory, be differentiated into any cell type, making them a powerful in vitro model for human biology. Recent technological advances have facilitated large-scale hPS cell studies that allow investigation of the genetic regulation of molecular phenotypes and their contribution to high-order phenotypes such as human disease.
HuM195 and its single-chain variable fragment increase Aβ phagocytosis in microglia via elimination of CD33 inhibitory signaling - Molecular Psychiatry
Abstract CD33 is a transmembrane receptor expressed on cells of myeloid lineage and regulates innate immunity. CD33 is a risk factor for Alzheimer’s disease (AD) and targeting CD33 has been a promising strategy drug development. However, the mechanism of CD33’s action is poorly understood. Here we investigate the mechanism of anti-CD33 antibody HuM195 (Lintuzumab) and its single-chain variable fragment (scFv) and examine their therapeutic potential.
SARS-CoV-2 infection causes dopaminergic neuron senescence
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hPSC differentiation toward DA neurons Midbrain dopaminergic neuron differentiation were performed using H9, MEL1 and SNCA different copy numbers hPSCs, which include NURR1: GFP hPSC. hPSCs were grown on VTN-N (Thermo Fisher Scientific)-coated 6-well plates in E8-essential medium. Cells were maintained at 37°C, 5% CO2.
By Liuliu Yang, Manoj Nair, Oliver Harschnitz, Jiajun Zhu, Pengfei Wang, So Yeon Koo, Lauretta A. Lacko, Vasuretha Chandar, Yaron Bram, Tuo Zhang, Wei Zhang, Feng J He, Junjie Wu, Yaoxing Huang, Todd Evans, Maarten J Titulaer, Jochem Spoor, Marianna Bugiani, Robert Schwartz, David Ho, Lorenz Studer, Shuibing Chen, Chendong Pan
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Cell Stem Cell
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Lipid droplets are a metabolic vulnerability in melanoma - Nature Communications
Abstract Melanoma exhibits numerous transcriptional cell states including neural crest-like cells as well as pigmented melanocytic cells. How these different cell states relate to distinct tumorigenic phenotypes remains unclear. Here, we use a zebrafish melanoma model to identify a transcriptional program linking the melanocytic cell state to a dependence on lipid droplets, the specialized organelle responsible for lipid storage.
Transient inhibition of p53 enhances prime editing and cytosine base-editing efficiencies in human pluripotent stem cells - Nature Communications
Abstract Precise gene editing in human pluripotent stem cells (hPSCs) holds great promise for studying and potentially treating human diseases.
A nomenclature consensus for nervous system organoids and assembloids - Nature
Abstract Self-organizing three-dimensional cellular models derived from human pluripotent stem cells or primary tissue have great potential to provide insights into how the human nervous system develops, what makes it unique and how disorders of the nervous system arise, progress and could be treated.
Anatomic position determines oncogenic specificity in melanoma - Nature
Abstract Oncogenic alterations to DNA are not transforming in all cellular contexts1,2. This may be due to pre-existing transcriptional programmes in the cell of origin. Here we define anatomic position as a major determinant of why cells respond to specific oncogenes. Cutaneous melanoma arises throughout the body, whereas the acral subtype arises on the palms of the hands, soles of the feet or under the nails3.
Human stem cell models to study host-virus interactions in the central nervous system
Abstract Advancements in human pluripotent stem cell technology offer a unique opportunity for the neuroimmunology field to study host–virus interactions directly in disease-relevant cells of the human central nervous system (CNS). Viral encephalitis is most commonly caused by herpesviruses, arboviruses and enteroviruses targeting distinct CNS cell types and often leading to severe neurological damage with poor clinical outcomes.
Parkinson’s disease grafts benefit from well-timed growth factor
NEWS AND VIEWS 26 May 2020 Grafts of stem-cell-derived precursors of dopamine neurons could be used to treat Parkinson’s disease, but this approach has limitations. Injecting a growth factor three weeks after transplantation can overcome some of these limits. Lorenz Studer & Lorenz Studer is in the Developmental Biology Program and the Center for Stem Cell Biology, the Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
Human SNORA31 variations impair cortical neuron-intrinsic immunity to HSV-1 and underlie herpes simplex encephalitis - Nature Medicine
Abstract Herpes simplex virus-1 (HSV-1) encephalitis (HSE) is typically sporadic. Inborn errors of TLR3- and DBR1-mediated central nervous system cell-intrinsic immunity can account for forebrain and brainstem HSE, respectively.
Derivation of enteric neuron lineages from human pluripotent stem cells
Abstract The enteric nervous system (ENS) represents a vast network of neuronal and glial cell types that develops entirely from migratory neural crest (NC) progenitor cells. Considerable improvements in the understanding of the molecular mechanisms underlying NC induction and regional specification have recently led to the development of a robust method to re-create the process in vitro using human pluripotent stem cells (hPSCs).
NFIA is a gliogenic switch enabling rapid derivation of functional human astrocytes from pluripotent stem cells
Abstract The mechanistic basis of gliogenesis, which occurs late in human development, is poorly understood. Here we identify nuclear factor IA (NFIA) as a molecular switch inducing human glial competency. Transient expression of NFIA is sufficient to trigger glial competency of human pluripotent stem cell-derived neural stem cells within 5 days and to convert these cells into astrocytes in the presence of glial-promoting factors, as compared to 3–6 months using current protocols.
New ISSCR guidelines: clinical translation of stem cell research
The Lancet's Manifesto We at believe it is our moral imperative to empower research and to grow the social impact of science. Improving lives is the only end goal that matters, and research is only relevant when it has impact on human lives. We therefore select only the best research papers, based on their quality of work and the progression they bring: the best science for better lives. Find out more about The Lancet's vision
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