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Articles by Ivan Berest
The transcriptional regulator IκBζ is essential for ILC2 effector functions
Abstract Group 2 innate lymphoid cells (ILC2) are the sentinels that ensure tissue homeostasis and engage in the immune response to helminths by secreting type 2 cytokines. Here we show that IκBζ, an atypical member of the IκB family, controls basal IL-5 production by ILC2s and governs their effector program during helminth infection and asthma.
Single-cell ultra-high-throughput multiplexed chromatin and RNA profiling reveals gene regulatory dynamics - Nature Methods
Abstract Enhancers and transcription factors (TFs) are crucial in regulating cellular processes. Current multiomic technologies to study these elements in gene regulatory mechanisms lack multiplexing capability and scalability. Here we present single-cell ultra-high-throughput multiplexed sequencing (SUM-seq) for co-assaying chromatin accessibility and gene expression in single nuclei.
Peroxisomes are critical for a unique metabolic demand and survival of alveolar macrophages
Keywords innate immunity tissue-resident macrophages immunometabolism peroxisomes Research topic(s) CP: Immunology CP: Metabolism Introduction Tissue-resident macrophages (TRMs) are part of the innate immune system that act as immune sentinels to maintain tissue homeostasis and provide defense against pathogen invasion.1 They are strategically distributed among various tissues and are readily capable of metabolic adaptation to microenvironmental factors, such as limited fuel sources,...
IL-1 protects from fatal systemic candidiasis in mice by inhibiting oxidative phosphorylation and hypoxia - Nature Communications
Abstract Invasive C. albicans infections result in high mortality rates. While IL-1 is important to combat C. albicans infections, the underlying mechanisms remain unclear. Using global and conditional Il1r1 knockouts in mice, here we show that IL-1R signaling in non-hematopoietic cells in the kidney and brain is crucial for a protective response. In the kidney, endothelial IL-1R contributes to fungal clearance independent of neutrophil recruitment, while IL-1R in hematopoietic cells is dispensable.
Tuft cell IL-17RB restrains IL-25 bioavailability and reveals context-dependent ILC2 hypoproliferation - Nature Immunology
Abstract The tuft cell–group 2 innate lymphoid cell (ILC2) circuit orchestrates rapid type 2 responses upon detecting microbially derived succinate and luminal helminths. Our findings delineate key mechanistic steps involving IP3R2 engagement and Ca2+ flux, governing interleukin-25 (IL-25) production by tuft cells triggered by succinate detection. While IL-17RB has a pivotal intrinsic role in ILC2 activation, it exerts a regulatory function in tuft cells.
Active repression of cell fate plasticity by PROX1 safeguards hepatocyte identity and prevents liver tumorigenesis - Nature Genetics
Abstract Cell fate plasticity enables development, yet unlocked plasticity is a cancer hallmark. While transcription master regulators induce lineage-specific genes to restrict plasticity, it remains unclear whether plasticity is actively suppressed by lineage-specific repressors. Here we computationally predict so-called safeguard repressors for 18 cell types that block phenotypic plasticity lifelong.
Integrative Single-Cell RNA-Seq and ATAC-Seq Analysis of Human Developmental Hematopoiesis
Highlights • The epigenetic and transcriptional landscape of human fetal hematopoiesis • Blood stem cells differentiate into three distinct oligopotent progenitor populations • Changes in motif accessibility in blood stem cells precede transcriptional priming • Refined sorting strategy to isolate and enrich for human fetal blood stem cells Summary Regulation of hematopoiesis during human development remains poorly defined.
Quantification of Differential Transcription Factor Activity and Multiomics-Based Classification into Activators and Repressors: diffTF
Highlights • diffTF estimates differential TF activity based on chromatin data (basic mode) • Integration with RNA-seq identifies activator/repressor TFs (classification mode) • We applied diffTF to subtypes of CLL and hematopoietic differentiation • The TF classification was experimentally validated in both case studies Summary Transcription factors (TFs) regulate many cellular processes and can therefore serve as readouts of the signaling and regulatory state.
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