A5056450824- Single-cell and spatial transcriptomics
- Acute Myeloid Leukemia Research
- Immune cells in cancer
- Epigenetics and DNA Methylation
- Hematopoietic Stem Cell Transplantation
- Cancer Genomics and Diagnostics
- RNA modifications and cancer
- RNA Research and Splicing
- Cytokine Signaling Pathways and Interactions
- Virus-based gene therapy research
- Genomics and Chromatin Dynamics
- Viral Infectious Diseases and Gene Expression in Insects
- HER2/EGFR in Cancer Research
- Molecular Biology Techniques and Applications
- Fibroblast Growth Factor Research
- Advanced biosensing and bioanalysis techniques
- Cancer, Hypoxia, and Metabolism
- Glycosylation and Glycoproteins Research
- Advanced Biosensing Techniques and Applications
- Immune Cell Function and Interaction
- Plant Genetic and Mutation Studies
- Zebrafish Biomedical Research Applications
- Cancer-related molecular mechanisms research
- RNA Interference and Gene Delivery
- Neonatal Respiratory Health Research
Centre for Genomic Regulation
2018-2025
Universitat Pompeu Fabra
2018-2024
Institució Catalana de Recerca i Estudis Avançats
2024
Institute for Research in Biomedicine
2024
European Molecular Biology Laboratory
2014-2020
European Molecular Biology Organization
2015-2020
European Bioinformatics Institute
2013
DKFZ-ZMBH Alliance
2012
Heidelberg University
2012
Max Planck Society
1984-1987
Significance This study quantifies how protein levels are determined by the underlying 5′-UTR sequence of an mRNA. We accurately measured abundance in 2,041 variants, differing only positions −10 to −1. show that a few nucleotide substitutions can significantly alter expression. also developed predictive model explains two-thirds expression variation. provide convincing evidence key regulatory elements, including AUG context, mRNA secondary structure, and out-of-frame upstream AUGs...
Abstract Efficient preparation of high-quality sequencing libraries that well represent the biological sample is a key step for using next-generation in research. Tn5 enables fast, robust, and highly efficient processing limited input material while scaling to parallel hundreds samples. Here, we present robust transposase purification strategy based on an N-terminal His6-Sumo3 tag. We demonstrate prepared with our in-house are same quality as those processed commercially available kit...
Abstract Single-cell genomics technology has transformed our understanding of complex cellular systems. However, excessive cost and a lack strategies for the purification newly identified cell types impede their functional characterization large-scale profiling. Here, we have generated high-content single-cell proteo-genomic reference maps human blood bone marrow that quantitatively link expression up to 197 surface markers identities biological processes across all main hematopoietic in...
Inter-patient variability and the similarity of healthy leukemic stem cells (LSCs) have impeded characterization LSCs in acute myeloid leukemia (AML) their differentiation landscape. Here, we introduce CloneTracer, a novel method that adds clonal resolution to single-cell RNA-seq datasets. Applied samples from 19 AML patients, CloneTracer revealed routes differentiation. Although residual preleukemic dominated dormant cell compartment, active resembled counterpart retained erythroid...
Cancer stem cells drive disease progression and relapse in many types of cancer. Despite this, a thorough characterization these remains elusive with it the ability to eradicate cancer at its source. In acute myeloid leukemia (AML), leukemic (LSCs) underlie mortality but are difficult isolate due their low abundance high similarity healthy hematopoietic (HSCs). Here, we demonstrate that LSCs, HSCs, pre-leukemic can be identified molecularly profiled by combining single-cell transcriptomics...
Abstract Following gastrulation, the three primary germ layers develop into major organs in a process known as organogenesis. Single-cell RNA sequencing has enabled profiling of gene expression dynamics these cell fate decisions, yet comprehensive map interplay between transcription factors and cis-regulatory elements is lacking, are underlying regulatory networks. Here we generate multi-omics atlas mouse early organogenesis by simultaneously chromatin accessibility from tens thousands...
Abstract The induction of central T cell tolerance in the thymus depends on presentation peripheral self-epitopes by medullary thymic epithelial cells (mTECs). This promiscuous gene expression (pGE) drives mTEC transcriptomic diversity, with non-canonical transcript initiation, alternative splicing, and endogenous retroelements (EREs) representing important but incompletely understood contributors. Here we map genome-wide transcripts immature mature human mTECs using high-throughput 5’ cap...
Summary Current approaches to lineage tracing of stem cell clones require genetic engineering or rely on sparse somatic DNA variants, which are difficult capture at single-cell resolution. Here, we show that targeted measurements methylation single-CpG resolution deliver joint information about cellular differentiation state and clonal identities. We develop EPI-clone, a droplet-based method for transgene-free tracing, apply it study hematopoiesis, capturing hundreds trajectories across...
Article3 June 2015Open Access Single-cell polyadenylation site mapping reveals 3′ isoform choice variability Lars Velten European Molecular Biology Laboratory, Genome Unit, Heidelberg, Germany Search for more papers by this author Simon Anders Aleksandra Pekowska Aino I Järvelin Wolfgang Huber Vicent Pelechano M Steinmetz Corresponding Author Stanford Technology Center, Palo Alto, CA, USA Department of Genetics, University School Medicine, Stanford, Information Velten1, Anders1, Pekowska1,...
Donor blood saves lives, yet the potential impact of recurrent large-volume phlebotomy on donor health and hematopoietic stem cells (HSCs) remains largely unexplored. In our study, we conducted a comprehensive screening 217 older male volunteer donors with history extensive donation (>100 life-time donations) to investigate phenomenon clonal hematopoiesis (CH). No significant difference in overall incidence CH was found frequent (FD) compared sporadic (<10 donations, 212...
Relapse remains a major challenge in the clinical management of acute myeloid leukemia (AML) and is driven by rare therapy-resistant stem cells (LSCs) that reside specific bone marrow niches. Hypoxia signaling maintains quiescent metabolically relaxed state, desensitizing them to chemotherapy. This suggests hypothesis hypoxia contributes chemoresistance AML-LSCs may represent therapeutic target sensitize Here, we identify HIF
Abstract Single-cell DNA methylation profiling currently suffers from excessive noise and/or limited cellular throughput. We developed scTAM-seq, a targeted bisulfite-free method for up to 650 CpGs in 10,000 cells per experiment, with dropout rate as low 7%. demonstrate that scTAM-seq can resolve dynamics across B-cell differentiation blood and bone marrow, identifying intermediate states were previously masked. additionally queries surface-protein expression, thus enabling integration of...
Abstract Background The immune system has a central role in preventing carcinogenesis. Alteration of systemic cell levels may increase cancer risk. However, the extent to which common genetic variation influences blood traits and risk remains largely undetermined. Here, we identify pleiotropic variants predict their underlying molecular cellular alterations. Methods Multivariate Cox regression was used evaluate associations between diagnosis cases UK Biobank. Shared were identified from...
Understanding the molecular and cellular processes involved in lung epithelial regeneration may fuel development of therapeutic approaches for diseases. We combine mouse models allowing diphtheria toxin-mediated damage specific cell types parallel GFP-labeling functionally dividing cells with single-cell transcriptomics to characterize distal lung. uncover types, including Krt13
Abstract For decades, studies have noted that transcription factors (TFs) can behave as either activators or repressors of different target genes. More recently, evidence suggests TFs act on simultaneously in positive and negative ways. Here we use biophysical models gene regulation to define, conceptualize explore these two aspects TF action: “duality”, where be overall both at the level transcriptional response, “coherent incoherent” modes regulation, mechanistically a given an activator...
Abstract Single cell RNA sequencing (scRNA-seq) data is widely used to study cancer states and their heterogeneity. However, the tumour microenvironment usually a mixture of healthy cancerous cells it can be difficult fully separate these two populations based on transcriptomics alone. If available, somatic single nucleotide variants (SNVs) observed in scRNA-seq could identify population. calling SNVs challenging task, as most seen short read are not somatic, but instead germline variants,...
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Clonal cell population dynamics play a critical role in both disease and development. Due to high mitochondrial mutation rates under healthy diseased conditions, genomic variability is particularly useful resource facilitating the identification of clonal structure. Here we present mitoClone2, an all-inclusive R package allowing for populations through integration heteroplasmic variants discovered from single-cell sequencing experiments. Our streamlines investigation this phenomenon by...