Stuart H. Orkin

RNA Editors Sculpt the Transcriptome During Terminal Erythropoiesis

The paper identifies ZCCHC6 and DIS3L2 as key regulators of RNA decay during terminal erythropoiesis, showing their role in post-transcriptional globin switching and {gamma}-globin stabilization.

Gene editing without ex vivo culture evades genotoxicity in human hematopoietic stem cells

This study shows that gene editing of HSCs without ex vivo culture reduces genotoxicity while maintaining therapeutic efficacy for beta-hemoglobinopathy treatment.

Structural Insights into the DNA-Binding Mechanism of BCL11A: The Integral Role of ZnF6

This study investigates the DNA-binding mechanism of BCL11A, revealing the role of ZnF6 in repression of {gamma}-globin gene expression and its implications for therapeutic design.

Integrated genomic analysis of AgRP neurons reveals that IRF3 regulates leptin's hunger-suppressing effects

The paper identifies IRF3 as a key transcriptional regulator of leptin's hunger-suppressing effects in AgRP neurons through integrated genomic analysis.

Rapid-kinetics degron benchmarking reveals off-target activities and mixed agonism-antagonism of MYB inhibitors

The paper benchmarks six MYB inhibitors using a nascent transcriptomics assay, revealing partial specificity, off-target activity, and mixed agonism-antagonism effects.

Matrin3 mediates differentiation through stabilizing chromatin accessibility and chromatin loop-domain interactions, and YY1 mediated enhancer-promoter interactions

The paper shows Matrin3 stabilizes chromatin accessibility and loop-domain interactions, and facilitates YY1-mediated enhancer-promoter interactions during differentiation.

Leukemia core transcriptional circuitry is a sparsely interconnected hierarchy stabilized by incoherent feed-forward loops

The paper reconstructs a sparsely interconnected transcriptional hierarchy in leukemia cells stabilized by incoherent feed-forward loops and shows inhibitors disrupt core regulators' programs.

Transcriptional plasticity drives leukemia immune escape

The paper identifies transcription factors regulating MHC-II expression in AML and shows their role in immune evasion and relapse.

High-efficiency HDR in immortalized cell lines by crude rAAV mediated donor template delivery

This study demonstrates high-efficiency HDR-mediated knock-in of large DNA fragments in human and mouse cell lines using crude rAAV without purification.

A distinct core regulatory module enforces oncogene expression in KMT2A-rearranged leukemia

The paper identifies a modular core regulatory circuitry in AML that enforces oncogene expression in KMT2A-rearranged leukemias.

Developmental maturation of the hematopoietic system controlled by a Lin28b-let-7-PRC1 axis

The paper identifies a Lin28b-let-7-PRC1 axis that regulates hematopoietic maturation across development, with Cbx2 playing a key role in controlling developmental timing of hematopoietic transcription factors.

A saturating mutagenesis CRISPR-Cas9 mediated functional genomic screen identifies cis- and trans-regulatory elements of Oct4 in embryonic stem cells

The paper identifies cis- and trans-regulatory elements of Oct4 in mESCs using ctSCAN-SMS, showing CREs are more active and conserved than TREs.

Histone demethylome map reveals combinatorial gene regulatory functions in embryonic stem cells

The paper identifies combinatorial functions of histone demethylases in gene regulation of mouse embryonic stem cells by analyzing their genome-wide binding patterns.

An engineered CRISPR/Cas9 mouse line for simultaneous readout of lineage histories and gene expression profiles in single cells

The paper introduces a CRISPR/Cas9 mouse line (CARLIN) to simultaneously track lineage histories and gene expression in single cells, revealing clonal bottlenecks in hematopoietic stem cells.

CUT&RUNTools: a flexible pipeline for CUT&RUN processing and footprint analysis

CUT&RUNTools processes CUT&RUN data to identify protein binding and genomic footprints through read analysis and visualization.

Enhancer-dependence of gene expression increases with developmental age

The paper shows that enhancer-dependence of gene expression increases with developmental age in mouse and human cells.

CRISPR-SURF: Discovering regulatory elements by deconvolution of CRISPR tiling screen data

CRISPR-SURF deconvolves CRISPR tiling screen data to identify functional regulatory elements across CRISPR-Cas, CRISPRi, and CRISPRa experiments.

The Polycomb-dependent epigenome controls β-cell dysfunction, dedifferentiation and diabetes

This study identifies chromatin-state signatures linked to β-cell dysfunction and diabetes by combining epigenome mapping with single-cell transcriptomics in mice and humans.

Integrated design, execution, and analysis of arrayed and pooled CRISPR genome editing experiments

The paper presents a protocol for designing, executing, and analyzing CRISPR genome editing experiments using CRISPOR and CRISPResso.

Dissecting super-enhancer hierarchy based on chromatin interactions

The paper identifies hub enhancers within super-enhancers using Hi-C and ChIP-seq data, showing their role in gene activation and chromatin structure.

Challenges And Emerging Directions In Single-Cell Analysis

This paper discusses challenges and future directions in single-cell analysis, highlighting advances in technologies and computational methods for studying cellular heterogeneity.