@article{ae6f4e887ed94fb2bd1154975be3e43d,
title = "Single-Cell Analyses Reveal Megakaryocyte-Biased Hematopoiesis in Myelofibrosis and Identify Mutant Clone-Specific Targets",
abstract = "Myelofibrosis (MF) is characterized by increased numbers of morphologically abnormal megakaryocytes (Mks). Single-cell RNA sequencing of >120,000 hematopoietic stem and progenitor cells demonstrated Mk-biased hematopoiesis across clinical and molecular MF subgroups. Mk progenitors were heterogeneous, with distinct expression of inflammatory mediators. Aberrant surface G6B expression on MF stem and progenitors could allow selective immunotherapeutic targeting of the MF clone.",
keywords = "G6B, TARGET-seq, bone marrow, fibrosis, immunotherapy, megakaryopoiesis, myeloproliferative neoplasm, platelets, single-cell multi-omics",
author = "{NIH Intramural Sequencing Center} and Bethan Psaila and Guanlin Wang and Alba Rodriguez-Meira and Rong Li and Heuston, {Elisabeth F.} and Lauren Murphy and Daniel Yee and Hitchcock, {Ian S.} and Nikolaos Sousos and Jennifer O'Sullivan and Stacie Anderson and Senis, {Yotis A.} and Weinberg, {Olga K.} and Calicchio, {Monica L.} and Deena Iskander and Daniel Royston and Dragana Milojkovic and Irene Roberts and Bodine, {David M.} and Supat Thongjuea and Mead, {Adam J.}",
note = "Funding Information: We thank all the patients who kindly donated samples; Dr. Sally-Ann Clark and others in the MRC WIMM Flow Cytometry facility; Dr. Michalina Mazurczyk in the Mass Spectrometry Facility and Dr. Neil Ashley in the MRC WIMM Single Cell Facility; Dr. Alice Young in the NIH Intramural Sequencing Center; the NHGRI Flow Cytometry facility; the University of York Imaging and Cytometry facility; and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC). This work was funded by a Cancer Research UK Advanced Clinician Scientist Fellowship and CRUK Innovation Award; a Wellcome Career Development Fellowship; an Academy of Medical Sciences Award and a L'Or?al-UNESCO Women in Science Award to B.P.; a Medical Research Council (MRC) Senior Clinical Fellowship, CRUK Early Detection Project Grant and CRUK Senior Cancer Research Fellowship to A.J.M.; Bloodwise and LAB282 (project grants to B.P. and A.J.M.); a Cancer Research UK DPhil Prize Studentship to A.R.-M.; a MRC John Fell Fund award and the MRC Molecular Haematology Unit core award to A.J.M.; and an MRC John Fell Fund award to B.P. and A.J.M. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, the Department of Health, or the NIH. B.P. designed, performed, and analyzed experiments; performed bioinformatic analyses; and wrote the manuscript. G.W. participated in experimental planning and designed, developed, and performed bioinformatic analyses. A.R.-M. designed, performed, and analyzed TARGET-seq experiments and performed bioinformatic analyses. E.F.H. performed experiments and contributed to bioinformatic analyses. R.L. L.M. J.O. and N.S. performed experiments, processed samples, and analyzed data. S.A. performed experiments. Y.A.S. contributed the G6B antibody and interpreted data. D.Y. and I.S.H. performed and analyzed antibody internalization experiments. O.K.W. D.R. and M.L.C. performed the immunohistochemical staining and analyses. D.I. performed experiments and assisted with protocol development. D.M. contributed clinical samples and data interpretation. I.R. and D.M.B. helped to supervise the project. S.T. designed, developed, and supervised the computational data analysis and wrote the manuscript. A.J.M. supervised the project, designed experiments, interpreted data, and wrote the manuscript. All authors read and approved the submitted manuscript. The authors declare no relevant competing interests. Funding Information: We thank all the patients who kindly donated samples; Dr. Sally-Ann Clark and others in the MRC WIMM Flow Cytometry facility; Dr. Michalina Mazurczyk in the Mass Spectrometry Facility and Dr. Neil Ashley in the MRC WIMM Single Cell Facility; Dr. Alice Young in the NIH Intramural Sequencing Center; the NHGRI Flow Cytometry facility; the University of York Imaging and Cytometry facility; and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC). This work was funded by a Cancer Research UK Advanced Clinician Scientist Fellowship and CRUK Innovation Award ; a Wellcome Career Development Fellowship ; an Academy of Medical Sciences Award and a L{\textquoteright}Or{\'e}al-UNESCO Women in Science Award to B.P.; a Medical Research Council (MRC) Senior Clinical Fellowship , CRUK Early Detection Project Grant and CRUK Senior Cancer Research Fellowship to A.J.M.; Bloodwise and LAB282 (project grants to B.P. and A.J.M.); a Cancer Research UK DPhil Prize Studentship to A.R.-M.; a MRC John Fell Fund award and the MRC Molecular Haematology Unit core award to A.J.M.; and an MRC John Fell Fund award to B.P. and A.J.M. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, the Department of Health, or the NIH. Publisher Copyright: {\textcopyright} 2020 The Authors",
year = "2020",
month = may,
day = "7",
doi = "10.1016/j.molcel.2020.04.008",
language = "English (US)",
volume = "78",
pages = "477--492.e8",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "3",
}