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The transition from quiescent to activated states in human hematopoietic stem cells is governed by dynamic 3D genome reorganization

To elucidate the epigenetic changes which occur when human long-term hematopoietic stem cells (LT-HSC) become activated we performed Bulk ATAC-Seq on 13 sorted bulk hematopoietic populations from cord bloodas well as single-cell ATAC-Seq upon CD34+CD38-CD45RA- cells enriched for HSC as well as CD34+/CD38+ progenitor cells both from cord blood. These studies revealed gains of chromatin accessibility around CTCF binding sites during HSPC activation, as such we additionally performed Low-C to directly profile the 3D conformation of human cord-blood derived LT-HSC and Short-term hematopoietic stem cells (ST-HSC), as well as Hi-C , ATAC-Seq and CTCF ChIP-Seq upon the OCIAML-2 cell line in which CTCF sites gained during LT-HSC activation are enriched. Finally we transduced human cord-blood LT-HSC with an shCTCF vector; in-vitro cultured LT-HSC cells harbouring shCTCF were used to perform RNA-Seq, and scATAC-Seq was performed on CD34+/CD38- human CB cells transduced with shCTCF, four weeks post xeno-transplantation into mice. Collectively these studies have helped us demonstrate the role of 3D chromatin conformation changes during human LT-HSC activation.

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Access to data generated by UHN is made available by completing the data access agreement for review by the data access committee and will be granted to qualified investigators for appropriate use.

DATA ACCESS AGREEMENT These terms and conditions govern access to the managed access datasets (details of which are set out in Appendix I) to which the User Institution has requested access. The User Institution agrees to be bound by these terms and conditions. Definitions Authorised Personnel: The individuals at the User Institution to whom the Data Access Committee (DAC) grants access to the Data. This includes the User, the individuals listed in Appendix II and any other individuals for whom the User Institution subsequently requests access to the Data. Details of the initial Authorised Personnel are set out in Appendix II. Data: The managed access datasets to which the User Institution has requested access. Data Producers: The Principal Investigator and the collaborators listed in Appendix I responsible for the development, organisation, and oversight of these Data. External Collaborator: A collaborator of the User, working for an institution other than the User Institution. Project: The project for which the User Institution has requested access to these Data. A description of the Project is set out in Appendix II. Publications: Includes, without limitation, articles published in print journals, electronic journals, reviews, books, posters and other written and verbal presentations of research. Research Participant: An individual whose data form part of these Data. Research Purposes: Shall mean research that is seeking to advance the understanding of genetics and genomics, including the treatment of disorders, and work on statistical methods that may be applied to such research. User: The principal investigator for the Project. User Institution(s): The Institution that has requested access to the Data. University Health Network: The University Health Network (UHN) is the largest clinical and research hospital in Canada. UHN is affiliated with the University of Toronto and is a member of the Toronto Academic Health Science Network. 1. The User Institution agrees to only use these Data for the purpose of the Project (described in Appendix II) and only for Research Purposes. The User Institution further agrees that it will only use these Data for Research Purposes which are within the limitations (if any) set out in Appendix I. 2. The User Institution agrees to preserve, at all times, the confidentiality of these Data. In particular, it undertakes not to use, or attempt to use these Data to compromise or otherwise infringe the confidentiality of information on Research Participants. Without prejudice to the generality of the foregoing, the User Institution agrees to use at least the measures set out in Appendix I to protect these Data. 3. The User Institution agrees to protect the confidentiality of Research Participants in any research papers or publications that they prepare by taking all reasonable care to limit the possibility of identification. 4. The User Institution agrees not to link or combine these Data to other information or archived data available in a way that could re-identify the Research Participants, even if access to that data has been formally granted to the User Institution or is freely available without restriction. 5. The User Institution agrees only to transfer or disclose these Data, in whole or part, or any material derived from these Data, to the Authorised Personnel. Should the User Institution wish to share these Data with an External Collaborator, the External Collaborator must complete a separate application for access to these Data. 6. The User Institution agrees that the Data Producers, and all other parties involved in the creation, funding or protection of these Data: a) make no warranty or representation, express or implied as to the accuracy, quality or comprehensiveness of these Data; b) exclude to the fullest extent permitted by law all liability for actions, claims, proceedings, demands, losses (including but not limited to loss of profit), costs, awards damages and payments made by the Recipient that may arise (whether directly or indirectly) in any way whatsoever from the Recipient’s use of these Data or from the unavailability of, or break in access to, these Data for whatever reason and; c) bear no responsibility for the further analysis or interpretation of these Data. 7. The User Institution agrees to follow the Fort Lauderdale Guidelines (http://www.wellcome.ac.uk/stellent/groups/corporatesite/@policy_communications/documents/web_document/wtd003207.pdf ) and the Toronto Statement (http://www.nature.com/nature/journal/v461/n7261/full/461168a.html). This includes but is not limited to recognising the contribution of the Data Producers and including a proper acknowledgement in all reports or publications resulting from the use of these Data. 8. The User Institution agrees to follow the Publication Policy in Appendix III. This includes respecting the moratorium period for the Data Producers to publish the first peer-reviewed report describing and analysing these Data. 9. The User Institution agrees not to make intellectual property claims on these Data and not to use intellectual property protection in ways that would prevent or block access to, or use of, any element of these Data, or conclusion drawn directly from these Data. 10. The User Institution can elect to perform further research that would add intellectual and resource capital to these data and decide to obtain intellectual property rights on these downstream discoveries. In this case, the User Institution agrees to implement licensing policies that will not obstruct further research and to follow the U.S. National Institutes of Health Best Practices for the Licensing of Genomic Inventions (2005) (https://www.icgc.org/files/daco/NIH_BestPracticesLicensingGenomicInventions_2005_en.pdf ) in conformity with the Organisation for Economic Co-operation and Development Guidelines for the Licensing of the Genetic Inventions (2006) (http://www.oecd.org/science/biotech/36198812.pdf ). 11. The User Institution agrees to destroy/discard the Data held, once it is no longer used for the Project, unless obliged to retain the data for archival purposes in conformity with audit or legal requirements. 12. The User Institution will notify the DAC within 30 days of any changes or departures of Authorised Personnel. 13. The User Institution will notify the DAC prior to any significant changes to the protocol for the Project. 14. The User Institution will notify the DAC as soon as it becomes aware of a breach of the terms or conditions of this agreement. 15. The DAC may terminate this agreement by written notice to the User Institution. If this agreement terminates for any reason, the User Institution will be required to destroy any Data held, including copies and backup copies. This clause does not prevent the User Institution from retaining these data for archival purpose in conformity with audit or legal requirements. 16. The User Institution accepts that it may be necessary for the Data Producers to alter the terms of this agreement from time to time. In the event that changes are required, the Data Producers or their appointed agent will contact the User Institution to inform it of the changes and the User Institution may elect to accept the changes or terminate the agreement. 17. If requested, the User Institution will allow data security and management documentation to be inspected to verify that it is complying with the terms of this agreement. 18. The User Institution agrees to distribute a copy of these terms to the Authorised Personnel. The User Institution will procure that the Authorised Personnel comply with the terms of this agreement. 19. This agreement (and any dispute, controversy, proceedings or claim of whatever nature arising out of this agreement or its formation) shall be construed, interpreted and governed by the laws of the province of Ontario and PHIPA. Agreed for User Institution Signature: Name: Title: Date: Principal Investigator I confirm that I have read and understood this Agreement. Signature: Name: Title: Date: Agreed for The Data Access Committee Signature: Name: Title: Date: APPENDIX I – DATASET DETAILS APPENDIX II ––PROJECT DETAILS APPENDIX III –– PUBLICATION POLICY

Studies are experimental investigations of a particular phenomenon, e.g., case-control studies on a particular trait or cancer research projects reporting matching cancer normal genomes from patients.

Study ID Study Title Study Type
Epigenetics
Epigenetics
Epigenetics
Epigenetics
Epigenetics
RNASeq

This table displays only public information pertaining to the files in the dataset. If you wish to access this dataset, please submit a request. If you already have access to these data files, please consult the download documentation.

ID File Type Size Located in
EGAF00004723944 bam 190.9 MB
EGAF00004723945 bam 190.2 MB
EGAF00004723946 bam 189.5 MB
EGAF00004723947 bam 190.1 MB
EGAF00004723948 bam 190.7 MB
EGAF00004723949 bam 189.8 MB
EGAF00004723950 bam 191.7 MB
EGAF00004723951 bam 191.6 MB
EGAF00004723952 bam 191.6 MB
EGAF00004723953 bam 191.2 MB
EGAF00004723954 bam 191.8 MB
EGAF00004723955 bam 191.4 MB
EGAF00004723956 bam 191.1 MB
EGAF00004723957 fastq.gz 5.8 GB
EGAF00004723958 fastq.gz 4.3 GB
EGAF00004723959 fastq.gz 4.2 GB
EGAF00004723960 fastq.gz 1.5 GB
EGAF00004723961 fastq.gz 3.1 GB
EGAF00004723962 fastq.gz 3.4 GB
EGAF00004723963 fastq.gz 5.7 GB
EGAF00004723964 fastq.gz 3.4 GB
EGAF00004723965 fastq.gz 4.1 GB
EGAF00004723966 fastq.gz 8.1 GB
EGAF00004723967 fastq.gz 6.2 GB
EGAF00004723968 fastq.gz 5.4 GB
EGAF00004723969 fastq.gz 7.4 GB
EGAF00004723970 fastq.gz 1.4 GB
EGAF00004723971 fastq.gz 3.3 GB
EGAF00004723972 fastq.gz 3.8 GB
EGAF00004723973 fastq.gz 5.0 GB
EGAF00004723974 fastq.gz 3.5 GB
EGAF00004723975 fastq.gz 5.0 GB
EGAF00004723976 fastq.gz 3.1 GB
EGAF00004723977 fastq.gz 2.0 GB
EGAF00004723978 fastq.gz 778.7 MB
EGAF00004723979 fastq.gz 2.5 GB
EGAF00004723980 fastq.gz 5.1 GB
EGAF00004723981 fastq.gz 2.5 GB
EGAF00004723982 fastq.gz 6.0 GB
EGAF00004723983 fastq.gz 4.6 GB
EGAF00004723984 fastq.gz 2.3 GB
EGAF00004723985 fastq.gz 6.3 GB
EGAF00004723986 fastq.gz 6.6 GB
EGAF00004723987 fastq.gz 5.5 GB
EGAF00004723988 bam 3.4 GB
EGAF00004723989 bam 3.9 GB
EGAF00004723990 bam 3.6 GB
EGAF00004723991 bam 3.1 GB
EGAF00004723992 bam 18.7 GB
EGAF00004723993 bam 26.4 GB
EGAF00004723994 bam 17.0 GB
EGAF00004723995 bam 3.0 GB
EGAF00004723996 bam 5.5 GB
EGAF00004723997 fastq.gz 2.6 GB
EGAF00004723998 fastq.gz 6.2 GB
EGAF00004723999 fastq.gz 2.4 GB
EGAF00004724000 fastq.gz 4.9 GB
EGAF00004724001 fastq.gz 2.4 GB
EGAF00004724002 fastq.gz 5.4 GB
EGAF00005296558 1620897248871 2.7 GB
EGAF00005296559 1620897309312 2.4 GB
EGAF00005296560 1620897427309 4.3 GB
EGAF00005296561 1620897248871 2.0 GB
EGAF00005296562 1620897187628 1.7 GB
EGAF00005296563 1620897187628 1.8 GB
EGAF00005296564 1620897248871 1.8 GB
EGAF00005296565 1620902948464 83.9 GB
EGAF00005296566 1620904008027 85.2 GB
EGAF00005296567 1620897187628 1.5 GB
EGAF00005296568 1620897187628 1.7 GB
EGAF00005296569 1620897187628 1.7 GB
EGAF00005296570 1620897187628 1.8 GB
EGAF00005296571 1620897488632 3.5 GB
EGAF00005296572 1620897427308 3.6 GB
EGAF00005296573 1620897488631 3.7 GB
EGAF00005296574 1620897547913 3.8 GB
EGAF00005296575 1620897427309 3.2 GB
EGAF00005296576 1620897427310 3.2 GB
EGAF00005296577 1620897488631 3.4 GB
EGAF00005296578 1620897488631 3.5 GB
EGAF00005296579 1620897547913 3.5 GB
EGAF00005296580 1620897547913 3.5 GB
EGAF00005296581 1620897488631 3.3 GB
EGAF00005296582 1620897547913 3.5 GB
84 Files (476.9 GB)