iPSC-derived myelinoids to study myelin biology of humans.
iPSC-derived myelinoids to study myelin biology of humans.
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DOI：
10.1016/j.devcel.2021.04.006
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发表时间：
2021-05-03
影响因子：
11.8
通讯作者：
Chandran S
中科院分区：
文献类型：
--
作者：
James OG;Selvaraj BT;Magnani D;Burr K;Connick P;Barton SK;Vasistha NA;Hampton DW;Story D;Smigiel R;Ploski R;Brophy PJ;Ffrench-Constant C;Lyons DA;Chandran S
髓鞘形成对中枢神经系统(CNS)的形成、健康和功能是必不可少的。健康和疾病中少突胶质细胞异质性的新证据以及小鼠和人类之间不同的CNS基因表达谱支持开发实验上易处理的人类髓鞘形成系统。在这里，我们开发了人IPSC来源的髓鞘有机体(“髓鞘”)和定量工具，以研究从少突发生到致密髓鞘形成和有髓轴突组织的髓鞘形成。使用患者来源的细胞，我们模拟了一种有髓轴突的单基因疾病(NFasc155缺陷)，重述了结旁轴突-神经胶质连接形成受损的情况。我们还验证了髓鞘在单个少突胶质细胞水平和整个髓鞘细胞水平上用于髓鞘形成的药理学评估，并证明了髓鞘形成减少是对受抑制的突触小泡释放的反应。我们的研究提供了一个研究人类髓鞘发育、疾病和适应性髓鞘形成的平台。一种广泛而致密的髓鞘形成的人类干细胞来源的类器官模型，概括了患者来源的培养中受损的旁阳极形成。少突胶质细胞形态和全局髓鞘水平的药理学调节阻止突触小泡的释放导致髓鞘减少。描述一个人类干细胞衍生的致密髓鞘形成的定量模型，它概括了有髓轴突的结构组织。他们使用患者来源的细胞显示了受损的旁阳极形成，开发了分析髓鞘少突胶质细胞形态和全局髓鞘形成的方法，并证明了由于突触小泡释放减少而导致的髓鞘减少。
Myelination is essential for central nervous system (CNS) formation, health, and function. Emerging evidence of oligodendrocyte heterogeneity in health and disease and divergent CNS gene expression profiles between mice and humans supports the development of experimentally tractable human myelination systems. Here, we developed human iPSC-derived myelinating organoids (“myelinoids”) and quantitative tools to study myelination from oligodendrogenesis through to compact myelin formation and myelinated axon organization. Using patient-derived cells, we modeled a monogenetic disease of myelinated axons (Nfasc155 deficiency), recapitulating impaired paranodal axo-glial junction formation. We also validated the use of myelinoids for pharmacological assessment of myelination—both at the level of individual oligodendrocytes and globally across whole myelinoids—and demonstrated reduced myelination in response to suppressed synaptic vesicle release. Our study provides a platform to investigate human myelin development, disease, and adaptive myelination. A human stem cell-derived organoid model of widespread and compact myelination Recapitulated impaired paranode formation in patient-derived cultures Pharmacological modulation of oligodendrocyte morphology and global myelin levels Blocking synaptic vesicle release leads to hypomyelination James et al. describe a human stem cell-derived quantitative model of compact myelination that recapitulates structural organization of myelinated axons. They show impaired paranode formation using patient-derived cells, develop methods to analyze myelinating oligodendrocyte morphology and global myelination, and demonstrate hypomyelination in response to reduced synaptic vesicle release.
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影响因子：
11
作者：
Kelly S;Jahanshad N;Zalesky A;Kochunov P;Agartz I;Alloza C;Andreassen OA;Arango C;Banaj N;Bouix S;Bousman CA;Brouwer RM;Bruggemann J;Bustillo J;Cahn W;Calhoun V;Cannon D;Carr V;Catts S;Chen J;Chen JX;Chen X;Chiapponi C;Cho KK;Ciullo V;Corvin AS;Crespo-Facorro B;Cropley V;De Rossi P;Diaz-Caneja CM;Dickie EW;Ehrlich S;Fan FM;Faskowitz J;Fatouros-Bergman H;Flyckt L;Ford JM;Fouche JP;Fukunaga M;Gill M;Glahn DC;Gollub R;Goudzwaard ED;Guo H;Gur RE;Gur RC;Gurholt TP;Hashimoto R;Hatton SN;Henskens FA;Hibar DP;Hickie IB;Hong LE;Horacek J;Howells FM;Hulshoff Pol HE;Hyde CL;Isaev D;Jablensky A;Jansen PR;Janssen J;Jönsson EG;Jung LA;Kahn RS;Kikinis Z;Liu K;Klauser P;Knöchel C;Kubicki M;Lagopoulos J;Langen C;Lawrie S;Lenroot RK;Lim KO;Lopez-Jaramillo C;Lyall A;Magnotta V;Mandl RCW;Mathalon DH;McCarley RW;McCarthy-Jones S;McDonald C;McEwen S;McIntosh A;Melicher T;Mesholam-Gately RI;Michie PT;Mowry B;Mueller BA;Newell DT;O'Donnell P;Oertel-Knöchel V;Oestreich L;Paciga SA;Pantelis C;Pasternak O;Pearlson G;Pellicano GR;Pereira A;Pineda Zapata J;Piras F;Potkin SG;Preda A;Rasser PE;Roalf DR;Roiz R;Roos A;Rotenberg D;Satterthwaite TD;Savadjiev P;Schall U;Scott RJ;Seal ML;Seidman LJ;Shannon Weickert C;Whelan CD;Shenton ME;Kwon JS;Spalletta G;Spaniel F;Sprooten E;Stäblein M;Stein DJ;Sundram S;Tan Y;Tan S;Tang S;Temmingh HS;Westlye LT;Tønnesen S;Tordesillas-Gutierrez D;Doan NT;Vaidya J;van Haren NEM;Vargas CD;Vecchio D;Velakoulis D;Voineskos A;Voyvodic JQ;Wang Z;Wan P;Wei D;Weickert TW;Whalley H;White T;Whitford TJ;Wojcik JD;Xiang H;Xie Z;Yamamori H;Yang F;Yao N;Zhang G;Zhao J;van Erp TGM;Turner J;Thompson PM;Donohoe G
通讯作者：
Donohoe G
影响因子：
16.6
作者：
Castelijns, Bas;Baak, Mirna L.;Creyghton, Menno P.
通讯作者：
Creyghton, Menno P.
影响因子：
64.8
作者：
Fuenfschilling, Ursula;Supplie, Lotti M.;Mahad, Don;Boretius, Susann;Saab, Aiman S.;Edgar, Julia;Brinkmann, Bastian G.;Kassmann, Celia M.;Tzvetanova, Iva D.;Moebius, Wiebke;Diaz, Francisca;Meijer, Dies;Suter, Ueli;Hamprecht, Bernd;Sereda, Michael W.;Moraes, Carlos T.;Frahm, Jens;Goebbels, Sandra;Nave, Klaus-Armin
通讯作者：
Nave, Klaus-Armin
影响因子：
64.8
作者：
Hubler Z;Allimuthu D;Bederman I;Elitt MS;Madhavan M;Allan KC;Shick HE;Garrison E;T Karl M;Factor DC;Nevin ZS;Sax JL;Thompson MA;Fedorov Y;Jin J;Wilson WK;Giera M;Bracher F;Miller RH;Tesar PJ;Adams DJ
通讯作者：
Adams DJ
神经元活动会影响体内髓鞘形成的轴突选择。
影响因子：
25
作者：
Hines, Jacob H.;Ravanelli, Andrew M.;Schwindt, Rani;Scott, Ethan K.;Appel, Bruce
通讯作者：
Appel, Bruce