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Cell of Origin and Early Evolution of Leukemia in Down Syndrome

To investigate the mechanism by which GATA1s and STAG2 deficiency contribute to Down Syndrome leukemogenesis, specifically within the propagating CD34/CD117 cell fractions from primary xenografts, we carried out transcriptional and epigenetic profiling by RNAseq and ATACseq. The chromatin accessibility landscape was compared to bulk ATACseq of individually sorted N-FL HSPC subpopulations. To investigate the mechanism underlying the synergy between T21 and GATA1s in driving preleukemia development, we analyzed the binding occupancy of GATA1. We performed Cut&Run assays to profile genome-wide GATA1 binding sites and also to quantify binding changes upon GATA1s editing in N-FL and T21-FL CD34+ enriched HSPCs. Lastly, we profiled miRNAs from N-FL and T21-FL CD34+ enriched HSPCs by miRNA-Seq.

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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 ( ) and the Toronto Statement ( 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) ( ) in conformity with the Organisation for Economic Co-operation and Development Guidelines for the Licensing of the Genetic Inventions (2006) ( ). 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
EGAS00001004780 Other
ID File Type Size Located in
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EGAF00004833972 fastq.gz 2.9 GB
EGAF00004833973 fastq.gz 2.7 GB
EGAF00004833974 fastq.gz 2.8 GB
EGAF00004833975 fastq.gz 2.9 GB
EGAF00004833976 fastq.gz 2.9 GB
EGAF00004833977 fastq.gz 3.1 GB
EGAF00004833978 fastq.gz 3.2 GB
EGAF00004833979 fastq.gz 3.0 GB
EGAF00004833980 fastq.gz 3.1 GB
EGAF00004833981 fastq.gz 2.7 GB
EGAF00004833982 fastq.gz 2.9 GB
EGAF00004833983 fastq.gz 2.7 GB
EGAF00004833984 fastq.gz 2.8 GB
EGAF00004833985 fastq.gz 2.9 GB
EGAF00004833986 fastq.gz 3.0 GB
EGAF00004833987 fastq.gz 2.9 GB
EGAF00004833988 fastq.gz 3.1 GB
EGAF00004833989 fastq.gz 2.7 GB
EGAF00004833990 fastq.gz 2.8 GB
EGAF00004833991 fastq.gz 2.5 GB
EGAF00004833992 fastq.gz 2.6 GB
EGAF00004833993 fastq.gz 2.8 GB
EGAF00004833994 fastq.gz 2.9 GB
EGAF00004833995 fastq.gz 2.7 GB
EGAF00004833996 fastq.gz 2.8 GB
EGAF00004833997 fastq.gz 2.9 GB
EGAF00004833998 fastq.gz 3.0 GB
EGAF00004833999 fastq.gz 2.7 GB
EGAF00004834000 fastq.gz 2.8 GB
EGAF00004834001 fastq.gz 2.8 GB
EGAF00004834002 fastq.gz 2.9 GB
EGAF00004834003 fastq.gz 2.8 GB
EGAF00004834004 fastq.gz 2.9 GB
EGAF00004834005 fastq.gz 2.8 GB
EGAF00004834006 fastq.gz 2.8 GB
EGAF00004834007 fastq.gz 2.8 GB
EGAF00004834008 fastq.gz 2.9 GB
EGAF00004834009 fastq.gz 2.6 GB
EGAF00004834010 fastq.gz 2.8 GB
EGAF00004834011 fastq.gz 2.8 GB
EGAF00004834012 fastq.gz 2.9 GB
EGAF00004834013 fastq.gz 2.8 GB
EGAF00004834014 fastq.gz 2.9 GB
EGAF00004834015 fastq.gz 2.7 GB
EGAF00004834016 fastq.gz 2.8 GB
EGAF00004834017 fastq.gz 2.8 GB
EGAF00004834018 fastq.gz 2.8 GB
EGAF00004834019 fastq.gz 3.0 GB
EGAF00004834020 fastq.gz 3.2 GB
EGAF00004834021 fastq.gz 2.9 GB
EGAF00004834022 fastq.gz 3.0 GB
EGAF00004834023 fastq.gz 2.8 GB
EGAF00004834024 fastq.gz 3.0 GB
EGAF00004834025 fastq.gz 1.7 GB
EGAF00004834026 fastq.gz 1.7 GB
EGAF00004834027 fastq.gz 1.1 GB
EGAF00004834028 fastq.gz 1.2 GB
EGAF00004834029 fastq.gz 1.4 GB
EGAF00004834030 fastq.gz 1.4 GB
EGAF00004834031 fastq.gz 1.5 GB
EGAF00004834032 fastq.gz 1.5 GB
EGAF00004834033 fastq.gz 1.3 GB
EGAF00004834034 fastq.gz 1.3 GB
EGAF00004834035 fastq.gz 1.4 GB
EGAF00004834036 fastq.gz 1.4 GB
EGAF00004834037 fastq.gz 1.1 GB
EGAF00004834038 fastq.gz 1.2 GB
EGAF00004834039 fastq.gz 1.3 GB
EGAF00004834040 fastq.gz 1.3 GB
EGAF00004834041 bam 3.8 GB
EGAF00004834042 bam 2.7 GB
EGAF00004834043 bam 3.2 GB
EGAF00004834044 bam 3.6 GB
EGAF00004834045 bam 3.0 GB
EGAF00004834046 bam 3.3 GB
EGAF00004834047 bam 2.7 GB
EGAF00004834048 bam 3.1 GB
EGAF00004834049 fastq.gz 478.5 MB
EGAF00004834050 fastq.gz 361.8 MB
EGAF00004834051 fastq.gz 421.2 MB
EGAF00004834052 fastq.gz 413.2 MB
EGAF00004834053 fastq.gz 315.5 MB
EGAF00004834054 fastq.gz 446.3 MB
EGAF00004834055 bam 724.9 MB
EGAF00004834056 bam 572.3 MB
EGAF00004834057 bam 688.6 MB
EGAF00004834058 bam 694.7 MB
EGAF00004834059 bam 500.4 MB
EGAF00004834060 bam 727.0 MB
EGAF00004834061 fastq.gz 2.4 GB
EGAF00004834062 fastq.gz 2.4 GB
EGAF00004834063 fastq.gz 2.7 GB
EGAF00004834064 fastq.gz 2.8 GB
EGAF00004834065 fastq.gz 2.5 GB
EGAF00004834066 fastq.gz 2.5 GB
EGAF00004834067 fastq.gz 3.0 GB
EGAF00004834068 fastq.gz 3.1 GB
EGAF00004834069 fastq.gz 2.9 GB
EGAF00004834070 fastq.gz 2.8 GB
EGAF00004834071 fastq.gz 2.9 GB
EGAF00004834072 fastq.gz 3.0 GB
EGAF00004834073 fastq.gz 2.4 GB
EGAF00004834074 fastq.gz 2.4 GB
EGAF00004834075 fastq.gz 2.5 GB
EGAF00004834076 fastq.gz 2.6 GB
EGAF00004834077 fastq.gz 2.5 GB
EGAF00004834078 fastq.gz 2.6 GB
EGAF00004834079 fastq.gz 2.7 GB
EGAF00004834080 fastq.gz 2.8 GB
EGAF00004834081 fastq.gz 2.4 GB
EGAF00004834082 fastq.gz 2.5 GB
EGAF00004834083 fastq.gz 2.7 GB
EGAF00004834084 fastq.gz 2.7 GB
EGAF00004834085 fastq.gz 2.9 GB
EGAF00004834086 fastq.gz 3.0 GB
EGAF00004834087 fastq.gz 2.6 GB
EGAF00004834088 fastq.gz 2.7 GB
EGAF00004834089 fastq.gz 2.4 GB
EGAF00004834090 fastq.gz 2.4 GB
EGAF00004834091 fastq.gz 3.1 GB
EGAF00004834092 fastq.gz 3.2 GB
EGAF00004834093 fastq.gz 3.8 GB
EGAF00004834094 fastq.gz 3.9 GB
EGAF00004834095 fastq.gz 3.8 GB
EGAF00004834096 fastq.gz 3.7 GB
EGAF00004834097 fastq.gz 2.4 GB
EGAF00004834098 fastq.gz 2.3 GB
EGAF00004834099 fastq.gz 2.6 GB
EGAF00004834100 fastq.gz 2.7 GB
EGAF00004834101 fastq.gz 2.6 GB
EGAF00004834102 fastq.gz 2.6 GB
EGAF00004834103 fastq.gz 2.3 GB
EGAF00004834104 fastq.gz 2.4 GB
EGAF00004834105 fastq.gz 2.3 GB
EGAF00004834106 fastq.gz 2.4 GB
EGAF00004834107 fastq.gz 2.6 GB
EGAF00004834108 fastq.gz 2.7 GB
EGAF00004834109 fastq.gz 2.6 GB
EGAF00004834110 fastq.gz 2.7 GB
EGAF00004834111 fastq.gz 2.6 GB
EGAF00004834112 fastq.gz 2.6 GB
EGAF00004834113 fastq.gz 2.8 GB
EGAF00004834114 fastq.gz 2.7 GB
EGAF00004834115 fastq.gz 3.0 GB
EGAF00004834116 fastq.gz 3.0 GB
EGAF00004834117 fastq.gz 2.9 GB
EGAF00004834118 fastq.gz 2.8 GB
EGAF00004834119 fastq.gz 2.7 GB
EGAF00004834120 fastq.gz 2.8 GB
EGAF00004834121 fastq.gz 3.2 GB
EGAF00004834122 fastq.gz 3.3 GB
EGAF00004834123 fastq.gz 3.2 GB
EGAF00004834124 fastq.gz 3.2 GB
EGAF00004834125 fastq.gz 3.4 GB
EGAF00004834126 fastq.gz 3.5 GB
EGAF00004834127 fastq.gz 3.9 GB
EGAF00004834128 fastq.gz 4.0 GB
EGAF00004834129 fastq.gz 3.8 GB
EGAF00004834130 fastq.gz 4.0 GB
EGAF00004834131 fastq.gz 3.4 GB
EGAF00004834132 fastq.gz 3.5 GB
EGAF00004834133 fastq.gz 3.8 GB
EGAF00004834134 fastq.gz 3.9 GB
EGAF00004834135 fastq.gz 3.7 GB
EGAF00004834136 fastq.gz 3.8 GB
EGAF00004834137 fastq.gz 3.6 GB
EGAF00004834138 fastq.gz 3.8 GB
EGAF00004834139 fastq.gz 3.1 GB
EGAF00004834140 fastq.gz 3.2 GB
EGAF00004834141 fastq.gz 3.7 GB
EGAF00004834142 fastq.gz 3.8 GB
EGAF00004834143 fastq.gz 3.8 GB
EGAF00004834144 fastq.gz 3.9 GB
EGAF00004834145 fastq.gz 2.5 GB
EGAF00004834146 fastq.gz 2.5 GB
EGAF00004834147 fastq.gz 3.7 GB
EGAF00004834148 fastq.gz 3.8 GB
EGAF00004834149 fastq.gz 3.2 GB
EGAF00004834150 fastq.gz 3.3 GB
EGAF00004834151 fastq.gz 3.2 GB
EGAF00004834152 fastq.gz 3.2 GB
EGAF00004834153 fastq.gz 3.8 GB
EGAF00004834154 fastq.gz 3.9 GB
EGAF00004834155 fastq.gz 3.4 GB
EGAF00004834156 fastq.gz 3.5 GB
EGAF00004834157 fastq.gz 3.7 GB
EGAF00004834158 fastq.gz 3.8 GB
EGAF00004834159 fastq.gz 3.2 GB
EGAF00004834160 fastq.gz 3.2 GB
190 Files (512.3 GB)