@article{f1d8dc58e3ec40f18a1705d2834f04de,
title = "Oligodendrocyte Death in Pelizaeus-Merzbacher Disease Is Rescued by Iron Chelation",
abstract = "Pelizaeus-Merzbacher disease is a pediatric leukodystrophy causing oligodendrocyte cell death. Nobuta et al. show that mutations in human PLP1 gene cause iron-induced cell death through lipid peroxidation, abnormal iron metabolism, and hypersensitivity to free iron. Iron chelation rescues cell death, offering a therapeutic direction for a disease without current treatments.",
keywords = "ferroptosis, gene correction, induced pluripotent stem cells, iron chelation, leukodystrophy, myelination, oligodendrocyte, patient models",
author = "Hiroko Nobuta and Nan Yang and Ng, {Yi Han} and Marro, {Samuele G.} and Khalida Sabeur and Manideep Chavali and Stockley, {John H.} and Killilea, {David W.} and Walter, {Patrick B.} and Chao Zhao and Philip Huie and Goldman, {Steven A.} and Kriegstein, {Arnold R.} and Franklin, {Robin J.M.} and Rowitch, {David H.} and Marius Wernig",
note = "Funding Information: We would like to thank Daniel Morrison for assistance in electron microscopy, Nobuko Uchida for the human-specific STEM121 antibody, Brian Popko for advice on the manuscript, and Hideyuki Okano for human PMD iPSC lines. Members of the Wernig and Rowitch laboratories provided advice on experimental design and the manuscript. H.N. acknowledges postdoctoral fellowship support from the European Leukodystrophy Association and career transition fellowship support from the National Multiple Sclerosis Society . M.C. acknowledges funding support from Career Development Grant awarded by Cerebral Palsy Alliance Research Foundation Inc. This work was supported by funding from the National Multiple Sclerosis Society (to M.W. and D.R.), the European Leukodystrophy Association , the New York Stem Cell Foundation (to M.W.), Action Medical Research , the Adelson Medical Research Foundation , the National Institute for Health Research Cambridge Biomedical Research Centre , and the European Research Council (to D.R.). M.W. was a Tashia and John Morgridge Faculty Scholar at the Child Health Research Institute at Stanford. Funding Information: We would like to thank Daniel Morrison for assistance in electron microscopy, Nobuko Uchida for the human-specific STEM121 antibody, Brian Popko for advice on the manuscript, and Hideyuki Okano for human PMD iPSC lines. Members of the Wernig and Rowitch laboratories provided advice on experimental design and the manuscript. H.N. acknowledges postdoctoral fellowship support from the European Leukodystrophy Association and career transition fellowship support from the National Multiple Sclerosis Society. M.C. acknowledges funding support from Career Development Grant awarded by Cerebral Palsy Alliance Research Foundation Inc. This work was supported by funding from the National Multiple Sclerosis Society (to M.W. and D.R.), the European Leukodystrophy Association, the New York Stem Cell Foundation (to M.W.), Action Medical Research, the Adelson Medical Research Foundation, the National Institute for Health Research Cambridge Biomedical Research Centre, and the European Research Council (to D.R.). M.W. was a Tashia and John Morgridge Faculty Scholar at the Child Health Research Institute at Stanford. Conceptualization, M.W. and D.R.; Methodology, H.N. and N.Y.; Investigation, H.N. N.Y. Y.H.N. S.G.M. K.S. M.C. J.H.S. and P.H.; Writing ? Original Draft, H.N.; Writing ? Review & Editing, M.W. D.R. D.W.K. P.B.W. C.Z. S.A.G. A.R.K. and R.J.M.F.; Fund Acquisition, M.W. and D.R.; Supervision, H.N. The authors declare no competing interests. Funding Information: Animals were cardiacly perfused with 4% PFA containing 0.25% glutaldehyde. Alternative vibratome sections were kept for immunohistochemistry and EM, which were post-fixed in 4% glutaraldehyde for several days. Regions of interest determined by immunohistochemistry were micro-dissected, fixed in 2% osmium tetroxide and embedded in resin. Ultrathin sections were placed onto copper grids, stained with uranyl acetate and lead, and examined with a Hitachi H-600 or TEM 1400 Transmission Electron Microscopes. Use of TEM 1400 was supported by NIH grant SIG number 1S10RR02678001. Publisher Copyright: {\textcopyright} 2019",
year = "2019",
month = oct,
day = "3",
doi = "10.1016/j.stem.2019.09.003",
language = "English (US)",
volume = "25",
pages = "531--541.e6",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "4",
}