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Norway

PMID:31786140  

HOTTIP lncRNA Promotes Hematopoietic Stem Cell Self-Renewal Leading to AML-like Disease in Mice.

Huacheng Luo | Ganqian Zhu | Jianfeng Xu | Qian Lai | Bowen Yan | Ying Guo | Tsz Kan Fung | Bernd B Zeisig | Ya Cui | Jie Zha | Christopher Cogle | Fei Wang | Bing Xu | Feng-Chun Yang | Wei Li | Chi Wai Eric So | Yi Qiu | Mingjiang Xu | Suming Huang
Cancer cell | 2019

Long non-coding RNAs (lncRNAs) are critical for regulating HOX genes, aberration of which is a dominant mechanism for leukemic transformation. How HOX gene-associated lncRNAs regulate hematopoietic stem cell (HSC) function and contribute to leukemogenesis remains elusive. We found that HOTTIP is aberrantly activated in acute myeloid leukemia (AML) to alter HOXA-driven topologically associated domain (TAD) and gene expression. HOTTIP loss attenuates leukemogenesis of transplanted mice, while reactivation of HOTTIP restores leukemic TADs, transcription, and leukemogenesis in the CTCF-boundary-attenuated AML cells. Hottip aberration in mice abnormally promotes HSC self-renewal leading to AML-like disease by altering the homeotic/hematopoietic gene-associated chromatin signature and transcription program. Hottip aberration acts as an oncogenic event to perturb HSC function by reprogramming leukemic-associated chromatin and gene transcription.

Pubmed ID: 31786140

Associated grants

  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL141950
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK110108
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL144712
  • Agency: NCI NIH HHS, United States
    Id: R01 CA228140
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL145883
  • Agency: NCI NIH HHS, United States
    Id: R01 CA172408
  • Agency: NHGRI NIH HHS, United States
    Id: R01 HG007538
  • Agency: NCI NIH HHS, United States
    Id: R01 CA204044
  • Agency: Medical Research Council, United Kingdom
    Id: G0800892

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This is a list of tools and resources that we have found mentioned in this publication.


ChIP-seq (tool)

RRID:SCR_001237

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.

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Cuffdiff (tool)

RRID:SCR_001647

Software that estimates expression at transcript-level resolution and controls for variability evident across replicate libraries.

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GATK (tool)

RRID:SCR_001876

A software package to analyze next-generation resequencing data. The toolkit offers a wide variety of tools, with a primary focus on variant discovery and genotyping as well as strong emphasis on data quality assurance. Its robust architecture, powerful processing engine and high-performance computing features make it capable of taking on projects of any size. This software library makes writing efficient analysis tools using next-generation sequencing data very easy, and second it's a suite of tools for working with human medical resequencing projects such as 1000 Genomes and The Cancer Genome Atlas. These tools include things like a depth of coverage analyzers, a quality score recalibrator, a SNP/indel caller and a local realigner. (entry from Genetic Analysis Software)

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SAMTOOLS (tool)

RRID:SCR_002105

Original 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.

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Strelka (tool)

RRID:SCR_005109

Software for somatic single nucleotide variant (SNV) and small indel detection from sequencing data of matched tumor-normal samples. The method employs a novel Bayesian approach which represents continuous allele frequencies for both tumor and normal samples, whilst leveraging the expected genotype structure of the normal. This is achieved by representing the normal sample as a mixture of germline variation with noise, and representing the tumor sample as a mixture of the normal sample with somatic variation. A natural consequence of the model structure is that sensitivity can be maintained at high tumor impurity without requiring purity estimates. The method has superior accuracy and sensitivity on impure samples compared to approaches based on either diploid genotype likelihoods or general allele-frequency tests.

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SnpEff (tool)

RRID:SCR_005191

Genetic variant annotation and effect prediction software toolbox that annotates and predicts effects of variants on genes (such as amino acid changes). By using standards, such as VCF, SnpEff makes it easy to integrate with other programs.

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Bowtie (tool)

RRID:SCR_005476

Software ultrafast memory efficient tool for aligning sequencing reads. Bowtie is short read aligner.

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Picard (tool)

RRID:SCR_006525

Java toolset for working with next generation sequencing data in the BAM format.

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Miltenyi Biotec (tool)

RRID:SCR_008984

An Organization portal, Antibody supplier, Service resource,

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HOMER (tool)

RRID:SCR_010881

Software tools for Motif Discovery and next-gen sequencing analysis. Used for analyzing ChIP-Seq, GRO-Seq, RNA-Seq, DNase-Seq, Hi-C and numerous other types of functional genomics sequencing data sets. Collection of command line programs for unix style operating systems written in Perl and C++.

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TopHat (tool)

RRID:SCR_013035

Software tool for fast and high throughput alignment of shotgun cDNA sequencing reads generated by transcriptomics technologies. Fast splice junction mapper for RNA-Seq reads. Aligns RNA-Seq reads to mammalian-sized genomes using ultra high-throughput short read aligner Bowtie, and then analyzes mapping results to identify splice junctions between exons.TopHat2 is accurate alignment of transcriptomes in presence of insertions, deletions and gene fusions.

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Cufflinks (tool)

RRID:SCR_014597

Software tool for transcriptome assembly and differential expression analysis for RNA-Seq. Includes script called cuffmerge that can be used to merge together several Cufflinks assemblies. It also handles running Cuffcompare as well as automatically filtering a number of transfrags that are likely to be artifacts. If the researcher has a reference GTF file, the researcher can provide it to the script to more effectively merge novel isoforms and maximize overall assembly quality.

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Diagenode (tool)

RRID:SCR_014807

Commercial provider of equipment and resources for epigenetics research, biological sample preparation, and diagnostic assays. The products Diagenode provides include automation and semi-automation software, antibodies, reagents, kits, and shearing technologies.

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Bestus Bioinformaticus Duk (tool)

RRID:SCR_016969

Software tool for trimming and filtering sequencing data. Used to combine data quality related trimming, filtering, and masking operations into a single tool adapter. BBDuk2 allows multiple kmer based operations in a single pass.

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ELDA (tool)

RRID:SCR_018933

Software tool for limiting dilution analysis, with particular attention to needs of stem cell assays. Provides confidence intervals for all LDA data sets, including those with 0% or 100% responses. Other features include test of adequacy of single hit hypothesis, tests for frequency differences between multiple data sets, and ability to take advantage of cases where number of cells in sample is counted exactly.

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Agilent TapeStation Laptop (tool)

RRID:SCR_019547

TapeStation Laptop is used to standardize data acquisition and analysis.

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ATACseqQC (tool)

RRID:SCR_023103

Software R package for post alignment quality assessment of ATAC-seq data. Package also contains functions to preprocess aligned ATAC-seq data for subsequent peak calling.

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BiocGenerics (tool)

RRID:SCR_024226

Software R package defines many S4 generic functions used in Bioconductor.

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C57BL/6J (tool)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

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APC anti-mouse Ly-6A/E (Sca-1) (antibody)

RRID:AB_313348

This monoclonal targets Ly-6A/E

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KMT2A/MLL Antibody (antibody)

RRID:AB_2145479

This unknown targets KMT2A/MLL

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H3K9me2-human (antibody)

RRID:AB_1977531

This monoclonal targets H3K9me2

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HDAC1 antibody - ChIP Grade (antibody)

RRID:AB_305705

This polyclonal targets HDAC1 - ChIP Grade

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Stat5 (antibody)

RRID:AB_2737403

This monoclonal targets Stat5

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Dot1L Antibody (antibody)

RRID:AB_789636

This polyclonal targets Human DOT1L

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Phospho-Stat5 (Tyr694) Antibody (antibody)

RRID:AB_2315225

This polyclonal targets Phospho-Stat5 (Tyr694)

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RUNX1 / AML1 antibody - ChIP Grade (antibody)

RRID:AB_2184205

This polyclonal targets RUNX1 / AML1 antibody - ChIP Grade

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H3K79me2-human (antibody)

RRID:AB_303937

This polyclonal targets H3K79me2

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H3K4me3-human (antibody)

RRID:AB_1163444

This monoclonal targets H3K4me3

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WDR5 antibody - ChIP Grade (antibody)

RRID:AB_946146

This monoclonal targets WDR5

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CD16 (antibody)

RRID:AB_395805

This monoclonal targets CD16 (FcγRIII)

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OCI-AML-3 (cell line)

RRID:CVCL_1844

Cell line OCI-AML-3 is a Cancer cell line with a species of origin Homo sapiens (Human)

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MOLM-13 (cell line)

RRID:CVCL_2119

Cell line MOLM-13 is a Cancer cell line with a species of origin Homo sapiens (Human)

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HEK293T (cell line)

RRID:CVCL_0063

Cell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)

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