Jonathan S. Weissman

Pycea provides a toolkit for analyzing single-cell lineage tracing data, integrating with Scanpy and offering visualization and statistical methods for lineage trees.

This study uses DNA methylation-based epigenome editing to durably and reversibly silence genes in human hematopoietic stem cells, demonstrating its application in modulating platelet function.

The paper introduces an imaging-based pooled screening method to identify genetic perturbations and their effects on cell states and neighboring cells in intact tissues.

Prime-editing lineage trees for 16 mouse embryos (E7.5 to E10.0, >1.4 million cells) quantify fate restriction timing, progenitor numbers and lineage relationships, and are reproducible across replicate embryos.

The paper identifies resilience factors in aged mice using a genome-scale ORF screen, finding NKX2-5 variants that restore vision and reduce frailty.

The paper identifies a cell-state-dependent pathway for degrading ER-retained 60S ribosomal subunits through UFMylation loss and the action of TLSD1.

This study uses a deep-learning model to analyze scRNA-seq data and identifies how folate deficiency disrupts metabolic transitions in developing mouse neural ectoderm, leading to morphological defects.

This study uses spatial transcriptomics and lineage tracing to show how tumor subclones drive microenvironmental changes that promote metastasis in a mouse model.

A >50,000-element viral smORF library screened by growth, MHC-I, ER stress, Perturb-seq and mass spectrometry yields >2,000 active microproteins and shows EBV BNLF2b inhibits PKA by mimicry.

This study shows that low-heteroplasmy mitochondrial DNA mutations provide reliable clonal information, improving clonal reconstruction in human cells.

The paper develops a contrastive learning model to integrate scRNA-seq data and perturbation responses, revealing conserved and cell-type-specific cellular responses to genetic perturbations.

The paper identifies 25% of 7,264 non-canonical open reading frames (ncORFs) as producing translated gene products, supported by over 3,000 peptides from 3.8 billion mass spectra.

The paper uses sequential CRISPR activation screens to identify genes sufficient for viral entry into cells, demonstrating effectiveness with Ebola and rabies viruses.

This study uses GENEVA to analyze drug response variations in cancer cells, revealing mitochondrial activation's role in KRAS inhibition and EMT as a resistance mechanism.

MitoDrift models mitochondrial inheritance to enable high-precision lineage tracing in human tissues, revealing clonal dynamics and linking them to transcriptional and epigenetic programs.

The paper identifies a primed endothelial progenitor that requires VEGF/ERK inhibition to differentiate into vein endothelial cells, revealing a two-step process for vein development.

The paper constructs a multi-tissue lysosomal metabolite atlas in mice, revealing age-related accumulation of glycerophosphodiesters and cystine, linked to lysosomal storage disorders, and shows caloric restriction mitigates these changes in some tissues.

OSK factors rejuvenate aged RPE cells by activating a Tet2-independent oxidative resilience pathway through GSTA4, restoring vision and reversing age-related degeneration.

The paper integrates genetic, transcriptomic, and structural data to show that Ca2+ dysregulation via ATP2B2 missense variants contributes to neuropsychiatric disorders.

PEtracer maps cell state and lineage dynamics in vivo with high spatial resolution using prime editing and multimodal imaging.

The paper introduces TRADE, a statistical framework to detect transcriptome-wide differential expression effects from noisy Perturb-seq data, showing that many true effects are not statistically significant but detectable in aggregate.

The paper identifies a novel pathway for ATF4 translation activation through CARS loss, independent of eIF2α phosphorylation and mTOR signaling.

This study identifies CD47 as a more effective macrophage immune checkpoint than CD24 in cancer and develops bispecific antibodies to enhance macrophage-mediated tumor killing.

The paper develops a platform combining imaging and sequencing to study genetic perturbations in mouse liver, identifying regulators of hepatocyte zonation and liver unfolded protein response.

The paper introduces COMET, a high-throughput screening platform for identifying transcriptional modulators by testing combinatorial dCas9-based fusion proteins, and finds over 5800 significant hits that modulate transcription.

This paper introduces ReDeeM, a framework for detecting mtDNA mutations in single cells to improve lineage tracing, showing improved accuracy and reliability over existing methods.

This study identifies GPX4 as a conserved suppressor of cold-induced cell death through multi-species CRISPR screens in hibernators and non-hibernators.

The paper uses CRISPRi screens to identify the lncRNA LOUP as a regulator of macrophage differentiation and inflammatory signaling through epigenetic and peptide-mediated mechanisms.

The paper introduces a dual sgRNA library design for CRISPRi screens to identify genetic modifiers, showing improved sensitivity and specificity in detecting epistatic relationships.

This study uses Perturb-seq to functionally interrogate SARS-CoV-2 host factors in human lung epithelial cells, identifying key factors that influence infection and host response.