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Dichotomous regulation of lysosomes by MYC and TFEB controls hematopoietic stem cell fate

We show that lysosomes are antagonistically controlled by TFEB and MYC to balance catabolic and anabolic processes required for activating LT-HSC and guiding their lineage fate. TFEB-mediated induction of the endolysosomal pathway for membrane receptor degradation limits LT-HSC metabolic and mitogenic activation; this promotes quiescence and self-renewal and governs erythroid-myeloid commitment. By contrast, MYC engages biosynthetic processes while repressing lysosomal catabolism to drive LT-HSC activation. Collectively, our study identifies lysosomes as a central regulatory hub for proper and coordinated stem cell fate determination.

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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
EGAS00001004967 Other
EGAS00001004968 Other
EGAS00001004969 Other
EGAS00001004970 Other
EGAS00001004971 Other
EGAS00001005462 Other

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
EGAF00004973776 fastq.gz 6.6 GB
EGAF00004973777 fastq.gz 6.6 GB
EGAF00004973778 fastq.gz 5.7 GB
EGAF00004973779 fastq.gz 5.7 GB
EGAF00004973780 fastq.gz 4.4 GB
EGAF00004973781 fastq.gz 4.4 GB
EGAF00004973782 fastq.gz 5.4 GB
EGAF00004973783 fastq.gz 5.5 GB
EGAF00004973784 fastq.gz 2.4 GB
EGAF00004973785 fastq.gz 2.5 GB
EGAF00004973786 fastq.gz 5.9 GB
EGAF00004973787 fastq.gz 6.0 GB
EGAF00004973788 fastq.gz 5.0 GB
EGAF00004973789 fastq.gz 5.0 GB
EGAF00004973790 fastq.gz 4.3 GB
EGAF00004973791 fastq.gz 4.3 GB
EGAF00004973792 fastq.gz 7.1 GB
EGAF00004973793 fastq.gz 7.1 GB
EGAF00004973794 fastq.gz 5.8 GB
EGAF00004973795 fastq.gz 5.8 GB
EGAF00004973796 fastq.gz 5.7 GB
EGAF00004973797 fastq.gz 5.8 GB
EGAF00004973798 fastq.gz 5.6 GB
EGAF00004973799 fastq.gz 5.6 GB
EGAF00004973800 fastq.gz 6.7 GB
EGAF00004973801 fastq.gz 6.8 GB
EGAF00004973802 fastq.gz 5.4 GB
EGAF00004973803 fastq.gz 5.4 GB
EGAF00004973804 fastq.gz 6.7 GB
EGAF00004973805 fastq.gz 6.8 GB
EGAF00004973806 fastq.gz 5.3 GB
EGAF00004973807 fastq.gz 5.3 GB
EGAF00004973808 fastq.gz 5.7 GB
EGAF00004973809 fastq.gz 5.9 GB
EGAF00004973810 fastq.gz 7.8 GB
EGAF00004973811 fastq.gz 7.9 GB
EGAF00004973812 fastq.gz 7.6 GB
EGAF00004973813 fastq.gz 7.8 GB
EGAF00004973814 fastq.gz 5.6 GB
EGAF00004973815 fastq.gz 5.5 GB
EGAF00004973816 fastq.gz 6.1 GB
EGAF00004973817 fastq.gz 6.2 GB
EGAF00004973818 fastq.gz 4.4 GB
EGAF00004973819 fastq.gz 4.3 GB
EGAF00004973820 fastq.gz 5.8 GB
EGAF00004973821 fastq.gz 6.0 GB
EGAF00004973822 fastq.gz 5.4 GB
EGAF00004973823 fastq.gz 5.5 GB
EGAF00004973824 fastq.gz 6.6 GB
EGAF00004973825 fastq.gz 6.6 GB
EGAF00004973826 fastq.gz 6.6 GB
EGAF00004973827 fastq.gz 6.6 GB
EGAF00004973828 fastq.gz 2.5 GB
EGAF00004973829 fastq.gz 2.6 GB
EGAF00004973830 fastq.gz 6.3 GB
EGAF00004973831 fastq.gz 6.2 GB
EGAF00004973832 fastq.gz 4.9 GB
EGAF00004973833 fastq.gz 4.9 GB
EGAF00004973834 fastq.gz 6.5 GB
EGAF00004973835 fastq.gz 6.6 GB
EGAF00004973836 fastq.gz 5.6 GB
EGAF00004973837 fastq.gz 5.4 GB
EGAF00004973838 fastq.gz 5.7 GB
EGAF00004973839 fastq.gz 5.8 GB
EGAF00004973840 fastq.gz 5.2 GB
EGAF00004973841 fastq.gz 5.3 GB
EGAF00004973842 fastq.gz 4.8 GB
EGAF00004973843 fastq.gz 4.9 GB
EGAF00004973844 fastq.gz 5.3 GB
EGAF00004973845 fastq.gz 5.5 GB
EGAF00004973846 fastq.gz 5.8 GB
EGAF00004973847 fastq.gz 5.8 GB
EGAF00004973848 fastq.gz 5.3 GB
EGAF00004973849 fastq.gz 5.3 GB
EGAF00004973850 fastq.gz 5.1 GB
EGAF00004973851 fastq.gz 5.1 GB
EGAF00004973852 fastq.gz 6.0 GB
EGAF00004973853 fastq.gz 6.1 GB
EGAF00004973854 fastq.gz 6.2 GB
EGAF00004973855 fastq.gz 6.3 GB
EGAF00004973856 fastq.gz 6.2 GB
EGAF00004973857 fastq.gz 6.2 GB
EGAF00004973858 fastq.gz 6.5 GB
EGAF00004973859 fastq.gz 6.5 GB
EGAF00004973860 fastq.gz 6.2 GB
EGAF00004973861 fastq.gz 6.1 GB
EGAF00004973862 fastq.gz 6.1 GB
EGAF00004973863 fastq.gz 6.1 GB
EGAF00004973864 fastq.gz 2.7 GB
EGAF00004973865 fastq.gz 2.8 GB
EGAF00004973866 fastq.gz 6.3 GB
EGAF00004973867 fastq.gz 6.3 GB
EGAF00004973868 fastq.gz 5.7 GB
EGAF00004973869 fastq.gz 5.6 GB
EGAF00004973870 fastq.gz 7.1 GB
EGAF00004973871 fastq.gz 7.1 GB
EGAF00004973872 fastq.gz 6.5 GB
EGAF00004973873 fastq.gz 6.6 GB
EGAF00004973874 fastq.gz 6.9 GB
EGAF00004973875 fastq.gz 7.0 GB
EGAF00004973876 fastq.gz 4.4 GB
EGAF00004973877 fastq.gz 4.5 GB
EGAF00004973878 fastq.gz 7.5 GB
EGAF00004973879 fastq.gz 7.5 GB
EGAF00004973880 fastq.gz 2.0 GB
EGAF00004973881 fastq.gz 2.0 GB
EGAF00004973882 fastq.gz 5.1 GB
EGAF00004973883 fastq.gz 5.0 GB
EGAF00004973884 fastq.gz 6.5 GB
EGAF00004973885 fastq.gz 6.5 GB
EGAF00004973886 fastq.gz 5.4 GB
EGAF00004973887 fastq.gz 5.4 GB
EGAF00004973888 fastq.gz 5.4 GB
EGAF00004973889 fastq.gz 5.6 GB
EGAF00004973890 fastq.gz 2.4 GB
EGAF00004973891 fastq.gz 2.5 GB
EGAF00004973892 fastq.gz 5.4 GB
EGAF00004973893 fastq.gz 5.3 GB
EGAF00004973894 fastq.gz 5.8 GB
EGAF00004973895 fastq.gz 5.9 GB
EGAF00004973896 fastq.gz 4.9 GB
EGAF00004973897 fastq.gz 4.9 GB
EGAF00004973898 fastq.gz 4.4 GB
EGAF00004973899 fastq.gz 4.3 GB
EGAF00004973900 fastq.gz 5.7 GB
EGAF00004973901 fastq.gz 5.8 GB
EGAF00004973902 fastq.gz 5.8 GB
EGAF00004973903 fastq.gz 5.7 GB
EGAF00004973904 fastq.gz 5.5 GB
EGAF00004973905 fastq.gz 5.5 GB
EGAF00004973906 fastq.gz 5.8 GB
EGAF00004973907 fastq.gz 5.9 GB
EGAF00004973908 fastq.gz 5.4 GB
EGAF00004973909 fastq.gz 5.3 GB
EGAF00004973910 fastq.gz 5.1 GB
EGAF00004973911 fastq.gz 5.3 GB
EGAF00004973912 fastq.gz 5.3 GB
EGAF00004973913 fastq.gz 5.3 GB
EGAF00004973914 fastq.gz 5.8 GB
EGAF00004973915 fastq.gz 5.7 GB
EGAF00004973916 fastq.gz 5.5 GB
EGAF00004973917 fastq.gz 5.5 GB
EGAF00004973918 fastq.gz 6.2 GB
EGAF00004973919 fastq.gz 6.0 GB
EGAF00004973920 fastq.gz 6.8 GB
EGAF00004973921 fastq.gz 6.9 GB
EGAF00004973922 fastq.gz 5.7 GB
EGAF00004973923 fastq.gz 5.6 GB
EGAF00004973924 fastq.gz 5.3 GB
EGAF00004973925 fastq.gz 5.4 GB
EGAF00004973926 fastq.gz 5.9 GB
EGAF00004973927 fastq.gz 5.8 GB
EGAF00004973928 fastq.gz 4.4 GB
EGAF00004973929 fastq.gz 4.5 GB
EGAF00004973930 fastq.gz 2.0 GB
EGAF00004973931 fastq.gz 2.0 GB
EGAF00004973932 fastq.gz 5.8 GB
EGAF00004973933 fastq.gz 5.8 GB
EGAF00004973934 fastq.gz 6.1 GB
EGAF00004973935 fastq.gz 6.1 GB
EGAF00004973936 fastq.gz 6.1 GB
EGAF00004973937 fastq.gz 6.0 GB
EGAF00004973938 fastq.gz 7.3 GB
EGAF00004973939 fastq.gz 7.3 GB
EGAF00004973940 fastq.gz 5.5 GB
EGAF00004973941 fastq.gz 5.4 GB
EGAF00005347653 fastq.gz 711.3 MB
EGAF00005347654 fastq.gz 760.1 MB
EGAF00005347655 fastq.gz 819.4 MB
EGAF00005347656 fastq.gz 846.8 MB
EGAF00005347657 fastq.gz 862.2 MB
EGAF00005347658 fastq.gz 902.0 MB
EGAF00005347659 fastq.gz 745.9 MB
EGAF00005347660 fastq.gz 777.1 MB
EGAF00005347661 fastq.gz 724.0 MB
EGAF00005347662 fastq.gz 764.7 MB
EGAF00005347663 fastq.gz 797.0 MB
EGAF00005347664 fastq.gz 858.2 MB
178 Files (934.5 GB)