Rudolf Jaenisch
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View article: Oxidative Stress and Interferon Signaling Drive Differential Pathogenesis of Ancestral and Contemporary Zika Viruses in Human Cerebral Organoids
Oxidative Stress and Interferon Signaling Drive Differential Pathogenesis of Ancestral and Contemporary Zika Viruses in Human Cerebral Organoids Open
Neurotropic Zika viruses (ZIKV) cause serious human disease with pandemic potential. Pathogenesis severities resulting from Asian/American versus African ZIKV lineage infections range from mild to severe, respectively; however, mechanisms …
View article: Functional genomic dissection of MS risk loci reveals convergence of cis and trans gene regulatory mechanisms in microglia
Functional genomic dissection of MS risk loci reveals convergence of cis and trans gene regulatory mechanisms in microglia Open
Summary Neurological diseases (NDs) are a major source of unmet medical need, and translational insights have been hampered by complex underlying pathophysiologies and limitations of experimental models. Noncoding single nucleotide polymor…
View article: Rapid iPSC inclusionopathy models shed light on formation, consequence, and molecular subtype of α-synuclein inclusions
Rapid iPSC inclusionopathy models shed light on formation, consequence, and molecular subtype of α-synuclein inclusions Open
The heterogeneity of protein-rich inclusions and its significance in neurodegeneration is poorly understood. Standard patient-derived iPSC models develop inclusions neither reproducibly nor in a reasonable time frame. Here, we developed sc…
View article: SARS-CoV-2 infection of human pluripotent stem cell-derived vascular cells reveals smooth muscle cells as key mediators of vascular pathology during infection
SARS-CoV-2 infection of human pluripotent stem cell-derived vascular cells reveals smooth muscle cells as key mediators of vascular pathology during infection Open
Although respiratory symptoms are the most prevalent disease manifestation of infection by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), nearly 20% of hospitalized patients are at risk for thromboembolic events. This prothr…
View article: Epigenomics and single cell CRISPR screening to investigate the risk‐modifying role of microglia in Alzheimer’s disease and multiple sclerosis
Epigenomics and single cell CRISPR screening to investigate the risk‐modifying role of microglia in Alzheimer’s disease and multiple sclerosis Open
Background Alzheimer’s disease (AD) and other neurodegenerative diseases (NDs) cause substantial health‐related and economic burdens, but progress towards preventative or ameliorative treatments has been limited. Genome‐wide association st…
View article: Multi-species genome-wide CRISPR screens identify conserved suppressors of cold-induced cell death
Multi-species genome-wide CRISPR screens identify conserved suppressors of cold-induced cell death Open
Summary Cells must adapt to environmental changes to maintain homeostasis. One of the most striking environmental adaptations is entry into hibernation during which core body temperature can decrease from 37°C to as low at 4°C. How mammali…
View article: Multi-species genome-wide CRISPR screens identify conserved suppressors of cold-induced cell death
Multi-species genome-wide CRISPR screens identify conserved suppressors of cold-induced cell death Open
Summary Cells must adapt to environmental changes to maintain homeostasis. One of the most striking environmental adaptations is entry into hibernation during which core body temperature can decrease from 37°C to as low at 4°C. How mammali…
View article: Tuning porosity of macroporous hydrogels enables rapid rates of stress relaxation and promotes cell expansion and migration
Tuning porosity of macroporous hydrogels enables rapid rates of stress relaxation and promotes cell expansion and migration Open
Extracellular matrix (ECM) viscoelasticity broadly regulates cell behavior. While hydrogels can approximate the viscoelasticity of native ECM, it remains challenging to recapitulate the rapid stress relaxation observed in many tissues with…
View article: Abortive infection of bat fibroblasts with SARS-CoV-2
Abortive infection of bat fibroblasts with SARS-CoV-2 Open
Bats are tolerant to highly pathogenic viruses such as Marburg, Ebola, and Nipah, suggesting the presence of a unique immune tolerance toward viral infection. Here, we compared severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) i…
View article: Pharmacological inhibition of Fms-like kinase 3 (FLT3) promotes neuronal maturation and suppresses seizure in a mouse model
Pharmacological inhibition of Fms-like kinase 3 (FLT3) promotes neuronal maturation and suppresses seizure in a mouse model Open
Fms-like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase predominantly expressed in blood and brain cells. While the FLT3 signaling pathway has been extensively studied in blood cell development and leukemia, its role in the brain r…
View article: Mitochondrial dysfunction and increased reactive oxygen species production in MECP2 mutant astrocytes and their impact on neurons
Mitochondrial dysfunction and increased reactive oxygen species production in MECP2 mutant astrocytes and their impact on neurons Open
Studies on MECP2 function and its implications in Rett Syndrome (RTT) have traditionally centered on neurons. Here, using human embryonic stem cell (hESC) lines, we modeled MECP2 loss-of-function to explore its effects on astrocyte (AST) d…
View article: Rapid iPSC inclusionopathy models shed light on formation, consequence, and molecular subtype of α-synuclein inclusions
Rapid iPSC inclusionopathy models shed light on formation, consequence, and molecular subtype of α-synuclein inclusions Open
The heterogeneity of protein-rich inclusions and its significance in neurodegeneration is poorly understood. Standard patient-derived iPSC models develop inclusions neither reproducibly nor in a reasonable time frame. Here, we developed sc…
View article: Multi-species genome-wide CRISPR screens identify conserved suppressors of cold-induced cell death
Multi-species genome-wide CRISPR screens identify conserved suppressors of cold-induced cell death Open
Summary Cells must adapt to environmental changes to maintain homeostasis. One of the most striking environmental adaptations is entry into hibernation during which core body temperature can decrease from 37°C to as low at 4°C. How mammali…
View article: The A53T Mutation in α-Synuclein Enhances Proinflammatory Activation in Human Microglia Upon Inflammatory Stimulus
The A53T Mutation in α-Synuclein Enhances Proinflammatory Activation in Human Microglia Upon Inflammatory Stimulus Open
Our results indicate that A53T mutant human microglia display cell autonomous phenotypes that may worsen neuronal damage in early-onset PD.
View article: Human-specific paralogs of SRGAP2 induce neotenic features of microglia structural and functional maturation
Human-specific paralogs of SRGAP2 induce neotenic features of microglia structural and functional maturation Open
SUMMARY Microglia play key roles in shaping synaptic connectivity during neural circuits development. Whether microglia display human-specific features of structural and functional maturation is currently unknown. We show that the ancestra…
View article: Approaches to pandemic prevention – the chromatin vaccine
Approaches to pandemic prevention – the chromatin vaccine Open
Developing effective vaccines against viral infections have significant impacts on development, prosperity and well-being of human populations. Thus, successful vaccines such as smallpox and polio vaccines, have promoted global societal we…
View article: High‐throughput CRISPRi screening to investigate mechanisms underlying Alzheimer’s risk loci
High‐throughput CRISPRi screening to investigate mechanisms underlying Alzheimer’s risk loci Open
Background Alzheimer’s disease (AD) is a highly (60‐80%) heritable disease with 75 known genetic risk loci. Interestingly, preliminary data from human tissues suggests that these risk loci predominantly act through myeloid cells, implicati…
View article: Genomic and biological variation in bat IFNs: An antiviral treatment approach
Genomic and biological variation in bat IFNs: An antiviral treatment approach Open
Bat‐borne viruses have attracted considerable research, especially in relation to the Covid‐19 pandemic. Although bats can carry multiple zoonotic viruses that are lethal to many mammalian species, they appear to be asymptomatic to viral i…
View article: Low-cost camera-based estrous tracking enables transgenesis in<i>Peromyscus leucopus</i>, the primary reservoir for Lyme disease
Low-cost camera-based estrous tracking enables transgenesis in<i>Peromyscus leucopus</i>, the primary reservoir for Lyme disease Open
CRISPR/Cas9 technology has revolutionized the production of animal models by reducing experimental timelines, slashing costs and streamlining gene editing, leading to a rapid expansion in the number of unique models for the study of human …
View article: Complex haploinsufficiency in pluripotent cells yields somatic cells with DNA methylation abnormalities and pluripotency induction defects
Complex haploinsufficiency in pluripotent cells yields somatic cells with DNA methylation abnormalities and pluripotency induction defects Open
A complete knockout of a single key pluripotency gene may drastically affect embryonic stem cell function and epigenetic reprogramming. In contrast, elimination of only one allele of a single pluripotency gene is mostly considered harmless…
View article: The A53T mutation in α-synuclein enhances pro-inflammatory activation in human microglia
The A53T mutation in α-synuclein enhances pro-inflammatory activation in human microglia Open
Parkinson’s disease (PD) is characterized by the aggregation of α-synuclein into Lewy bodies and Lewy neurites in the brain. Microglia-driven neuroinflammation may contribute to neuronal death in PD, however the exact role of microglia rem…
View article: SARS-CoV-2 infection of human pluripotent stem cell-derived vascular cells reveals smooth muscle cells as key mediators of vascular pathology during infection
SARS-CoV-2 infection of human pluripotent stem cell-derived vascular cells reveals smooth muscle cells as key mediators of vascular pathology during infection Open
Although respiratory symptoms are the most prevalent disease manifestation of infection by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), nearly 20% of hospitalized patients are at risk for thromboembolic events. This prothr…
View article: Data from DNMT3B Expression Might Contribute to CpG Island Methylator Phenotype in Colorectal Cancer
Data from DNMT3B Expression Might Contribute to CpG Island Methylator Phenotype in Colorectal Cancer Open
Purpose: DNA methyltransferase-3B (DNMT3B) plays an important role in de novo CpG island methylation. Dnmt3b can induce colon tumor in mice with methylation in specific CpG islands. We hypothesized that cellular DNMT3B level might influenc…
View article: Supplementary Data from DNMT3B Expression Might Contribute to CpG Island Methylator Phenotype in Colorectal Cancer
Supplementary Data from DNMT3B Expression Might Contribute to CpG Island Methylator Phenotype in Colorectal Cancer Open
Supplementary Data from DNMT3B Expression Might Contribute to CpG Island Methylator Phenotype in Colorectal Cancer
View article: Supplementary Data from DNMT3B Expression Might Contribute to CpG Island Methylator Phenotype in Colorectal Cancer
Supplementary Data from DNMT3B Expression Might Contribute to CpG Island Methylator Phenotype in Colorectal Cancer Open
Supplementary Data from DNMT3B Expression Might Contribute to CpG Island Methylator Phenotype in Colorectal Cancer
View article: Data from DNMT3B Expression Might Contribute to CpG Island Methylator Phenotype in Colorectal Cancer
Data from DNMT3B Expression Might Contribute to CpG Island Methylator Phenotype in Colorectal Cancer Open
Purpose: DNA methyltransferase-3B (DNMT3B) plays an important role in de novo CpG island methylation. Dnmt3b can induce colon tumor in mice with methylation in specific CpG islands. We hypothesized that cellular DNMT3B level might influenc…
View article: Rett Syndrome astrocytes disrupt neuronal activity and cerebral organoid development through transfer of dysfunctional mitochondria
Rett Syndrome astrocytes disrupt neuronal activity and cerebral organoid development through transfer of dysfunctional mitochondria Open
Studies on the function of Methyl CpG binding protein 2 (MECP2) and the consequence of MECP2 deficiency and duplication have largely focused on neurons. The function of MECP2 in human glia, along with the comprehensive understanding of gli…