William C. Skarnes

iPSC Neurodegenerative Disease Initiative isogenic CAG repeat iPSC line for Huntingtons disease

The paper generates isogenic iPSC lines with CAG repeats and HTT KO for Huntington's disease study, showing differentiation potential and altered gene expression in neurons and astrocytes.

The Genetic Discovery (GeDi) resource: Deep characterization of a multi-ancestry panel of human reference iPSCs for functional genomic studies

Autism-associated SCN2A deficiency disrupts cortico-striatal circuitry in human brain assembloids

This study shows that SCN2A deficiency in human brain assembloids disrupts cortico-striatal circuitry by impairing axonal projections and synaptic transmission, leading to hyperexcitability.

Epilepsy-Associated SCN2A-L1342P Mutation Drives Network Hyperexcitability and Widespread Transcriptomic Changes in Human Cortical Organoids

This study investigates the effects of the SCN2A-L1342P mutation in human cortical organoids, finding increased neuronal excitability, enhanced synaptic transmission, and transcriptomic changes related to synaptic and developmental pathways.

Splicing of ultraconserved poison exons controls mitotic fidelity and stem cell viability

This study shows that ultraconserved poison exons regulate mitotic splicing fidelity and stem cell viability by controlling SR protein levels and splicing networks.

Neurodegeneration risk variants promote lysosomal TMEM106B fibrilaccumulation

The paper identifies TMEM106B fibril accumulation as a shared mechanism in neurodegeneration linked to genetic variants in TMEM106B and GRN.

The complete genome of the KOLF2.1J reference iPSC line

The paper generates and characterizes a custom genome assembly for the KOLF2.1J iPSC line to improve genomic analysis accuracy compared to standard references.

Prevention of Transgene Silencing During Human PluripotentStem Cell Differentiation

The paper identifies strategies to prevent transgene silencing during human pluripotent stem cell differentiation and introduces a robust vector construct.

A xeno-free protocol for rapid differentiation of human iPSC-derived microglia from the KOLF2.1J reference line.

This paper presents a xeno-free protocol to rapidly differentiate human iPSCs into microglia using the KOLF2.1J line, resulting in functional microglia with immune markers and phagocytic activity.

Triglyceride metabolism controls inflammation and APOE4-associated disease states in microglia

This study shows that triglyceride metabolism is essential for microglial activation and disease states in APOE4 microglia, with implications for modulating immune responses.

Dissecting the biological impact of GBA1 mutations using multi-omics in an isogenic setting

The paper investigates the biological impact of GBA1 mutations using multi-omics in isogenic iPSC lines, finding limited overlapping results across cell types and suggesting RNA-based quantitation may not be optimal for characterizing GCase mechanisms.

Human microglia in brain assembloids display region-specific diversity and respond to hyperexcitable neurons carrying SCN2A mutation

This study uses brain organoids and assembloids with microglia to show region-specific microglial diversity and their response to SCN2A mutation-induced neuronal hyperactivity.

Restoration of excitation/inhibition balance enhances neuronal signal-to-noise ratio and rescues social deficits in autism-associated Scn2a-deficiency

This study shows that restoring NaV1.2 expression in adulthood rescues social deficits and improves neuronal signal-to-noise ratio in Scn2a-deficient mice.

Generation of C9orf72 repeat knock-in iPSC lines for modelling ALS and FTD

The paper describes the generation and validation of C9orf72 repeat expansion knock-in iPSC lines for ALS and FTD research, showing they differentiate into neurons and display disease-related pathologies.

Near 100% genome editing efficiency with a one-step all RNA prime editing system in a human reporter iPSC line

The paper develops an all-RNA prime editing system achieving over 95% editing efficiency in human iPSCs with minimal off-target effects.

Human iPSC-derived microglia sense and dampen hyperexcitability of cortical neurons carrying the epilepsy-associated SCN2A-L1342P mutation

This study shows human iPSC-derived microglia detect and reduce hyperexcitability in neurons with the SCN2A-L1342P epilepsy mutation through morphological and calcium changes and reduced sodium channel current density.

Expression of ALS-PFN1 impairs vesicular degradation in iPSC-derived microglia

This study shows that ALS-linked PFN1 mutations impair vesicular degradation in iPSC-derived microglia by disrupting autophagy, which can be mitigated by Rapamycin.

A reference induced pluripotent stem cell line for large-scale collaborative studies

The paper identifies and characterizes a reference iPSC line, KOLF2.1J, for standardized use in collaborative studies across multiple differentiation protocols and assays.

Controlling homology-directed repair outcomes in human stem cells with dCas9

This paper improves Cas9 RNP editing in human stem cells to achieve high rates of biallelic homology-directed repair of SNVs by using dCas9 to block re-cutting and damage.

Severe deficiency of voltage-gated sodium channel NaV1.2 elevates neuronal excitability in adult mice

This study shows that severe NaV1.2 deficiency increases neuronal excitability in adult mice, challenging the current understanding of its role in autism and epilepsy.

Sodium channel Nav1.2-L1342P variant displaying complex biophysical properties renders hyperexcitability of cortical neurons derived fromhuman iPSCs

This study investigates the effects of the SCN2A L1342P variant in human iPSC-derived neurons, showing increased excitability and resistance to phenytoin, but responsiveness to PTx3.

Characterization of a gene-trap knockout mouse model of Scn2a encoding voltage-gated sodium channel Nav1.2

This paper characterizes a Scn2a gene trap knockout mouse model with reduced Nav1.2 expression, showing behavioral and physiological abnormalities associated with Scn2a deficiency.