A5004611595- Single-cell and spatial transcriptomics
- Epigenetics and DNA Methylation
- Acute Myeloid Leukemia Research
- Genomics and Chromatin Dynamics
- Zebrafish Biomedical Research Applications
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Immune Cell Function and Interaction
- Cancer Genomics and Diagnostics
- T-cell and B-cell Immunology
- Immune cells in cancer
- Gene Regulatory Network Analysis
- Chronic Myeloid Leukemia Treatments
- Cancer-related gene regulation
- RNA modifications and cancer
- Histone Deacetylase Inhibitors Research
- CRISPR and Genetic Engineering
- RNA Research and Splicing
- Cytokine Signaling Pathways and Interactions
- Neonatal Respiratory Health Research
- Protein Degradation and Inhibitors
- Angiogenesis and VEGF in Cancer
- RNA Interference and Gene Delivery
- Bioinformatics and Genomic Networks
- Gene expression and cancer classification
- Pluripotent Stem Cells Research
Wellcome/MRC Cambridge Stem Cell Institute
2014-2024
University of Cambridge
2014-2024
Medical Research Council
2012-2022
Stem Cell Institute
2016-2020
Saveetha University
2020
Wellcome Trust
2016
Inhibition of glycogen synthase kinase-3 (Gsk3) supports mouse embryonic stem cells (ESCs) by modulating Tcf3, but the critical targets downstream Tcf3 are unclear. We analyzed intersection between genome localization and transcriptome data sets to identify genes repressed Tcf3. Among these, manipulations Esrrb gave distinctive phenotypes in functional assays. Knockdown knockout eliminated response Gsk3 inhibition, causing extinction pluripotency markers loss colony forming capability....
Hematopoietic differentiation critically depends on combinations of transcriptional regulators controlling the development individual lineages. Here, we report genome-wide binding sites for five key hematopoietic transcription factors—GATA1, GATA2, RUNX1, FLI1, and TAL1/SCL—in primary human megakaryocytes. Statistical analysis 17,263 regions bound by at least one factor demonstrated that simultaneous all factors was most enriched pattern often occurred near known regulators. Eight genes not...
Highlights•Comprehensive genome-scale resource for studying embryonic blood cell specification•Genome-scale definition of cis elements driving differential gene expression•A regulatory network model hematopoiesis aiding reprogramming experiments•Analysis suggests a role TEAD factors in hematopoietic specificationSummaryMetazoan development involves the successive activation and silencing specific expression programs is driven by tissue-specific transcription programming chromatin landscape....
The extraembryonic yolk sac (YS) ensures delivery of nutritional support and oxygen to the developing embryo but remains ill-defined in humans. We therefore assembled a comprehensive multiomic reference human YS from 3 8 postconception weeks by integrating single-cell protein gene expression data. Beyond its recognized role as site hematopoiesis, we highlight roles metabolism, coagulation, vascular development, hematopoietic regulation. reconstructed emergence decline stem progenitor cells...
CODEX (http://codex.stemcells.cam.ac.uk/) is a user-friendly database for the direct access and interrogation of publicly available next-generation sequencing (NGS) data, specifically aimed at experimental biologists. In an era multi-centre genomic dataset generation, provides single where these samples are collected, uniformly processed vetted. The main drive to provide wider scientific community with instant high-quality NGS which, irrespective publishing laboratory, directly comparable....
Rationale: The ETS (E-26 transformation-specific) transcription factor ERG (ETS-related gene) is essential for endothelial homeostasis, driving expression of lineage genes and repressing proinflammatory genes. Loss associated with diseases including atherosclerosis. ERG’s homeostatic function lineage-specific, because aberrant in cancer oncogenic. molecular basis lineage-specific activity unknown. Transcriptional regulation specificity linked to enhancer clusters (super-enhancers)....
Article23 December 2015Open Access Source DataTransparent process Cytokine-induced megakaryocytic differentiation is regulated by genome-wide loss of a uSTAT transcriptional program Hyun Jung Park Cambridge Institute for Medical Research, Wellcome Trust/MRC Stem Cell Institute, Cambridge, UK Department Haematology, University Search more papers this author Juan Li Rebecca Hannah Simon Biddie Ana I Leal-Cervantes Kristina Kirschner David Flores Santa Cruz Veronika Sexl Pharmacology and...
Transcription factor (TF) networks determine cell-type identity by establishing and maintaining lineage-specific expression profiles, yet reconstruction of mammalian regulatory network models has been hampered a lack comprehensive functional validation interactions. Here, we report ChIP-Seq, transgenic reporter gene experimental data that have allowed us to construct an experimentally validated model for haematopoietic stem/progenitor cells (HSPCs). Model simulation coupled with subsequent...
A gradual restriction in lineage potential of multipotent stem/progenitor cells is a hallmark adult hematopoiesis, but the underlying molecular events governing these processes remain incompletely understood. Here, we identified robust expression leukemia-associated transcription factor hepatic leukemia (Hlf) normal hematopoietic progenitors, which was rapidly downregulated upon differentiation. Interference with its downregulation revealed Hlf as strong negative regulator lymphoid...
The interaction of transcription factors with specific DNA sequences is critical for activation gene expression programs. In endothelial cells (EC), the factor NF-κB important in switch from quiescence to activation, and tightly controlled avoid excessive inflammation organ damage. Here we describe a novel mechanism that controls EC. Erg, most highly expressed ETS member resting EC, by repressing proinflammatory expression. Focusing on intercellular adhesion molecule 1(ICAM)-1 as model,...
The JAK2 tyrosine kinase is a critical mediator of cytokine-induced signaling. It plays role in the nucleus, where it regulates transcription by phosphorylating histone H3 at 41 (H3Y41ph). We used chromatin immunoprecipitation coupled to massively parallel DNA sequencing (ChIP-seq) define genome-wide pattern H3Y41ph human erythroid leukemia cells. Our results indicate that located three distinct sites: (1) subset active promoters, overlaps with H3K4me3, (2) distal cis-regulatory elements,...
The transcriptional coactivator Cbp plays an important role in a wide range of cellular processes, including proliferation, differentiation, and apoptosis. Although studies have shown its requirement for hematopoietic stem cell (HSC) development, adult HSC maintenance, as well the molecular mechanisms underlying function, is not clear. Here, we demonstrate gradual loss phenotypic HSCs differentiation defects following conditional ablation during homeostasis. In addition, Cbp-deficient...