Journal article
Epigenetic modulators of B cell fate identified through coupled phenotype-transcriptome analysis
IY Kong, S Trezise, A Light, I Todorovski, GM Arnau, S Gadipally, D Yoannidis, KJ Simpson, X Dong, L Whitehead, JC Tempany, AJ Farchione, AA Sheikh, JR Groom, KL Rogers, MJ Herold, VL Bryant, ME Ritchie, SN Willis, RW Johnstone Show all
Cell Death and Differentiation | SPRINGERNATURE | Published : 2022
Abstract
High-throughput methodologies are the cornerstone of screening approaches to identify novel compounds that regulate immune cell function. To identify novel targeted therapeutics to treat immune disorders and haematological malignancies, there is a need to integrate functional cellular information with the molecular mechanisms that regulate changes in immune cell phenotype. We facilitate this goal by combining quantitative methods for dissecting complex simultaneous cell phenotypic effects with genomic analysis. This combination strategy we term Multiplexed Analysis of Cells sequencing (MAC-seq), a modified version of Digital RNA with perturbation of Genes (DRUGseq). We applied MAC-seq to scr..
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Grants
Awarded by University of Melbourne
Funding Acknowledgements
We would like to thank Lisa Reid, Rhiannan Crawley, Rebekah Meeny and Marina Patsis for animal husbandry. We would also like to thank Prof Guillaume Lessene for his input in MAC-seq study and manuscript and Lizzy Pijpers for her assistance with organizing the compounds for MAC-seq. We acknowledge Compounds Australia (Griffith University) for providing specialized compound management and logistics research services to the project. EDH was supported by an RD Wright career development fellowship (#1159488) from the National Health and Medical Research Council (NHMRC) of Australia and grants from The Leukemia & Lymphoma Society (#6552-18) and NHMRC (#1140187, #1165591). SLN is supported by an NHMRC Senior Research fellowship 1155342 and NHMRC project grant 1144905. VLB was supported by Sir Clive McPherson Family Research Fellowship and received grants from Rae Foundation to support this work. PDH was supported by an NHMRC Investigator fellowship (1176588), and this work was supported by a project grant from the NHMRC to support EDH, VLB and PDH (1127198). RWJ was supported by a grant from the Cancer Council Victoria, project grant support from the NHMRC (to RWJ), NHMRC Program (grant 454569 to RWJ), NHMRC Senior Principal Research Fellowship (to RWJ) and The Kids' Cancer Project (to RWJ and SJV). SJV was supported by a Rubicon Fellowship from the Netherlands Organization for Scientific Research (NWO, 019.161LW.017) and an NHMRC Emerging leader fellowship (1178339). We acknowledge support from the Peter MacCallum Cancer Centre Foundation and the Australian Cancer Research Foundation. MJH was supported by grants and fellowships from the NHMRC (Ideas Grants 1186575, Project Grants 1145728, 1143105, 1159658 and Fellowships 1156095), the Leukemia and Lymphoma Society of America (LLS SCOR 7015-18), the Cancer Council of Victoria (project grant 1147328 and Venture Grant). GMA was supported by Peter MacCallum Cancer Centre Foundation seed grant (ID #1739). SNW was supported by the Walter and Eliza Hall Trust Centenary Fellowship, an NHMRC Ideas grant 1184523 (SLN and SNW) and the Leukemia & Lymphoma Society-Snowdome Foundation-Leukaemia Foundation (LLS-SF-LF; 6592-20) Translational Research Program (TRP) (SLN and SNW). This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC Independent Research Institutes Infrastructure Support Scheme Grant 361646. The Victorian Centre for Functional Genomics (KJS) is funded by the Australian Cancer Research Foundation (ACRF), Phenomics Australia, through funding from the Australian Government's National Collaborative Research Infrastructure Strategy (NCRIS) program, the Peter MacCallum Cancer Centre Foundation and the University of Melbourne Research Collaborative Infrastructure Program.