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Epigenetic Memory Underlies Cell-Autonomous Heterogeneous Behavior of Hematopoietic Stem Cells.

Cell | 2016

Stem cells determine homeostasis and repair of many tissues and are increasingly recognized as functionally heterogeneous. To define the extent of-and molecular basis for-heterogeneity, we overlaid functional, transcriptional, and epigenetic attributes of hematopoietic stem cells (HSCs) at a clonal level using endogenous fluorescent tagging. Endogenous HSC had clone-specific functional attributes over time in vivo. The intra-clonal behaviors were highly stereotypic, conserved under the stress of transplantation, inflammation, and genotoxic injury, and associated with distinctive transcriptional, DNA methylation, and chromatin accessibility patterns. Further, HSC function corresponded to epigenetic configuration but not always to transcriptional state. Therefore, hematopoiesis under homeostatic and stress conditions represents the integrated action of highly heterogeneous clones of HSC with epigenetically scripted behaviors. This high degree of epigenetically driven cell autonomy among HSCs implies that refinement of the concepts of stem cell plasticity and of the stem cell niche is warranted.

Pubmed ID: 27863245 RIS Download

Associated grants

  • Agency: NIA NIH HHS, United States
    Id: K25 AG037596
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL131768

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


Gene Expression Omnibus (GEO) (tool)

RRID:SCR_005012

Functional genomics data repository supporting MIAME-compliant data submissions. Includes microarray-based experiments measuring the abundance of mRNA, genomic DNA, and protein molecules, as well as non-array-based technologies such as serial analysis of gene expression (SAGE) and mass spectrometry proteomic technology. Array- and sequence-based data are accepted. Collection of curated gene expression DataSets, as well as original Series and Platform records. The database can be searched using keywords, organism, DataSet type and authors. DataSet records contain additional resources including cluster tools and differential expression queries.

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Bowtie 2 (tool)

RRID:SCR_016368

Ultrafast and memory efficient tool for aligning sequencing reads to long reference sequences. Supports gapped, local, and paired end alignment modes. More suited to finding longer, gapped alignments in comparison with original Bowtie method.

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Addgene (tool)

RRID:SCR_002037

Non-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.

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RRID:AB_313391

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FVB-Tg(Col2a1-cre/ERT)KA3Smac/J (organism)

RRID:IMSR_JAX:006774

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B6.Cg-Tg(Mx1-cre)1Cgn/J (organism)

RRID:IMSR_JAX:003556

Mus musculus with name B6.Cg-Tg(Mx1-cre)1Cgn/J from IMSR.

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RRID:IMSR_JAX:000664

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RRID:SCR_001790

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HOMER (software resource)

RRID:SCR_010881

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DESeq (software resource)

RRID:SCR_000154

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TopHat (software resource)

RRID:SCR_013035

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Bowtie (software resource)

RRID:SCR_005476

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R Project for Statistical Computing (software resource)

RRID:SCR_001905

Software environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.

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FlowJo (software resource)

RRID:SCR_008520

Software for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.

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APC anti-mouse CD48 (antibody)

RRID:AB_571997

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APC anti-mouse CD48 (antibody)

RRID:AB_571997

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