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Studies in vertebrates have outlined conserved molecular control of definitive endoderm (END) development. However, recent work also shows that key molecular aspects of human END regulation differ even from rodents. Differentiation of human embryonic stem cells (ESCs) to END offers a tractable system to study the molecular basis of normal and defective human-specific END development. Here, we interrogated dynamics in chromatin accessibility during differentiation of ESCs to END, predicting DNA-binding proteins that may drive this cell fate transition. We then combined single-cell RNA-seq with parallel CRISPR perturbations to comprehensively define the loss-of-function phenotype of those factors in END development. Following a few candidates, we revealed distinct impairments in the differentiation trajectories for mediators of TGFβ signaling and expose a role for the FOXA2 transcription factor in priming human END competence for human foregut and hepatic END specification. Together, this single-cell functional genomics study provides high-resolution insight on human END development.
Pubmed ID: 30995470 RIS Download
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Set of software modules for performing common ChIP-seq data analysis tasks across the whole genome, including positional correlation analysis, peak detection, and genome partitioning into signal-rich and signal-poor regions. The tools are designed to be simple, fast and highly modular. Each program carries out a well defined data processing procedure that can potentially fit into a pipeline framework. ChIP-Seq is also freely available on a Web interface.
View all literature mentionsGlobal nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.
View all literature mentionsNon-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.
View all literature mentionsCollection of curated, non-redundant genomic DNA, transcript RNA, and protein sequences produced by NCBI. Provides a reference for genome annotation, gene identification and characterization, mutation and polymorphism analysis, expression studies, and comparative analyses. Accessed through the Nucleotide and Protein databases.
View all literature mentionsA comprehensive collection of human transcription factor binding sites models. DNA sequences of TF binding regions obtained by both pregenomic and high-throughput methods were collected from existing databases and other public data. The ChIPMunk software was used to construct positional weight matrices. Four motif discovery strategies were tested based on different motif shape priors including flat and periodic priors associated with DNA helix pitch. A quality rating was manually assigned to each model based on known binding preferences. An appropriate TFBS model was selected for each TF, with similar models selected for related TFs. In any case only one model per TF was selected unless there was additional evidence for two distinct binding models or different stable modes of dimerization. All TFBS models and initial binding segments data used for motif discovery were mapped to UniPROT IDs.
View all literature mentionsA next-generation web-based application that aims to provide an integrated solution for both visualization and analysis of deep-sequencing data, along with simple access to public datasets.
View all literature mentionsA commercial organization which provides assay technologies to isolate DNA, RNA, and proteins from any biological sample. Assay technologies are then used to make specific target biomolecules, such as the DNA of a specific virus, visible for subsequent analysis.
View all literature mentionsSoftware package for differential gene expression analysis based on the negative binomial distribution. Used for analyzing RNA-seq data for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates.
View all literature mentionsAlignment analysis software tool for comparative mapping between two genome assemblies or between two different genomes. It can cache intermediate results to speed a comparisons of multiple sequences.
View all literature mentionsSoftware as R package designed for QC, analysis, and exploration of single cell RNA-seq data. Enable users to identify and interpret sources of heterogeneity from single cell transcriptomic measurements, and to integrate diverse types of single cell data.
View all literature mentionsOriginal SAMTOOLS package has been split into three separate repositories including Samtools, BCFtools and HTSlib. Samtools for manipulating next generation sequencing data used for reading, writing, editing, indexing,viewing nucleotide alignments in SAM,BAM,CRAM format. BCFtools used for reading, writing BCF2,VCF, gVCF files and calling, filtering, summarising SNP and short indel sequence variants. HTSlib used for reading, writing high throughput sequencing data.
View all literature mentionsJava toolset for working with next generation sequencing data in the BAM format.
View all literature mentionsSoftware performing alignment of high-throughput RNA-seq data. Aligns RNA-seq reads to reference genome using uncompressed suffix arrays.
View all literature mentionsSoftware performing alignment of high-throughput RNA-seq data. Aligns RNA-seq reads to reference genome using uncompressed suffix arrays.
View all literature mentionsThis monoclonal targets Oct-3/4
View all literature mentionsThis polyclonal targets H3K27ac
View all literature mentionsThis polyclonal targets Human SOX17
View all literature mentionsThis polyclonal targets Human GAPDH
View all literature mentionsThis monoclonal targets HA-Tag
View all literature mentionsThis monoclonal targets CD326
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis monoclonal targets CDX-2
View all literature mentionsThis unknown targets Rabbit IgG (H+L)
View all literature mentionsThis polyclonal targets Human Prox1
View all literature mentionsThis polyclonal secondary targets Mouse IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis monoclonal targets HNF4 antibody [K9218] - ChIP Grade
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis unknown targets Rabbit IgG (H+L)
View all literature mentionsThis polyclonal targets HNF3beta/FOXA2
View all literature mentionsThis unknown targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal targets Histone H3, trimethyl (Lys27)
View all literature mentionsCell line HEK293T/17 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line WA01 is a Embryonic stem cell with a species of origin Homo sapiens
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal targets Human GAPDH
View all literature mentionsThis monoclonal targets CD326
View all literature mentionsThis monoclonal targets CDX-2
View all literature mentionsThis monoclonal targets HA-Tag
View all literature mentionsThis polyclonal targets H3K27ac
View all literature mentionsThis polyclonal targets HNF3beta/FOXA2
View all literature mentionsThis monoclonal targets HNF4 antibody [K9218] - ChIP Grade
View all literature mentionsThis monoclonal targets Oct-3/4
View all literature mentionsThis polyclonal targets Human Prox1
View all literature mentionsThis polyclonal targets Human SOX17
View all literature mentionsCell line HEK293T/17 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line WA01 is a Embryonic stem cell with a species of origin Homo sapiens
View all literature mentionsThis unknown targets Rabbit IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis unknown targets Rabbit IgG (H+L)
View all literature mentionsThis polyclonal secondary targets Mouse IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal targets Histone H3, trimethyl (Lys27)
View all literature mentionsThis unknown targets IgG (H+L)
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