Patient-derived iPSCs show premature neural differentiation and neuron type-specific phenotypes relevant to neurodevelopment.
Patient-derived iPSCs show premature neural differentiation and neuron type-specific phenotypes relevant to neurodevelopment.
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DOI:
10.1038/mp.2017.238
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发表时间:
2018-08
影响因子:
11
通讯作者:
Weiss LA
中科院分区:
文献类型:
--
作者:
Yeh E;Dao DQ;Wu ZY;Kandalam SM;Camacho FM;Tom C;Zhang W;Krencik R;Rauen KA;Ullian EM;Weiss LA
Ras/MAPK pathway signaling is a major participant in neurodevelopment, and evidence suggests that BRAF, a key Ras signal mediator, influences human behavior. We studied the role of the mutation BRAFQ257R, the most common cause of cardiofaciocutaneous syndrome (CFC), in an induced pluripotent stem cell (iPSC)-derived model of human neurodevelopment. In iPSC-derived neuronal cultures from CFC subjects, we observed decreased p-AKT and p-ERK1/2 compared to controls, as well as a depleted neural progenitor pool and rapid neuronal maturation. Pharmacological PI3K/AKT pathway manipulation recapitulated cellular phenotypes in control cells and attenuated them in CFC cells. CFC cultures displayed altered cellular subtype ratios and increased intrinsic excitability. Moreover, in CFC cells, Ras/MAPK pathway activation and morphological abnormalities exhibited cell subtype-specific differences. Our results highlight the importance of exploring specific cellular subtypes and of using iPSC models to reveal relevant human-specific neurodevelopmental events.
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影响因子:
30.8
作者:
Lee, S. Hong;Ripke, Stephan;Neale, Benjamin M.;Faraone, Stephen V.;Purcell, Shaun M.;Perlis, Roy H.;Mowry, Bryan J.;Thapar, Anita;Goddard, Michael E.;Witte, John S.;Absher, Devin;Agartz, Ingrid;Akil, Huda;Amin, Farooq;Andreassen, Ole A.;Anjorin, Adebayo;Anney, Richard;Anttila, Verneri;Arking, Dan E.;Asherson, Philip;Azevedo, Maria H.;Backlund, Lena;Badner, Judith A.;Bailey, Anthony J.;Banaschewski, Tobias;Barchas, Jack D.;Barnes, Michael R.;Barrett, Thomas B.;Bass, Nicholas;Battaglia, Agatino;Bauer, Michael;Bayes, Monica;Bellivier, Frank;Bergen, Sarah E.;Berrettini, Wade;Betancur, Catalina;Bettecken, Thomas;Biederman, Joseph;Binder, Elisabeth B.;Black, Donald W.;Blackwood, Douglas H. R.;Bloss, Cinnamon S.;Boehnke, Michael;Boomsma, Dorret I.;Breen, Gerome;Breuer, Rene;Bruggeman, Richard;Cormican, Paul;Buccola, Nancy G.;Buitelaar, Jan K.;Bunney, William E.;Buxbaum, Joseph D.;Byerley, William F.;Byrne, Enda M.;Caesar, Sian;Cahn, Wiepke;Cantor, Rita M.;Casas, Miguel;Chakravarti, Aravinda;Chambert, Kimberly;Choudhury, Khalid;Cichon, Sven;Cloninger, C. Robert;Collier, David A.;Cook, Edwin H.;Coon, Hilary;Cormand, Bru;Corvin, Aiden;Coryell, William H.;Craig, David W.;Craig, Ian W.;Crosbie, Jennifer;Cuccaro, Michael L.;Curtis, David;Czamara, Darina;Datta, Susmita;Dawson, Geraldine;Day, Richard;De Geus, Eco J.;Degenhardt, Franziska;Djurovic, Srdjan;Donohoe, Gary J.;Doyle, Alysa E.;Duan, Jubao;Dudbridge, Frank;Duketis, Eftichia;Ebstein, Richard P.;Edenberg, Howard J.;Elia, Josephine;Ennis, Sean;Etain, Bruno;Fanous, Ayman;Farmer, Anne E.;Ferrier, I. Nicol;Flickinger, Matthew;Fombonne, Eric;Foroud, Tatiana;Frank, Josef;Franke, Barbara;Fraser, Christine;Freedman, Robert;Freimer, Nelson B.;Freitag, Christine M.;Friedl, Marion;Frisen, Louise;Gallagher, Louise;Gejman, Pablo V.;Georgieva, Lyudmila;Gershon, Elliot S.;Geschwind, Daniel H.;Giegling, Ina;Gill, Michael;Gordon, Scott D.;Gordon-Smith, Katherine;Green, Elaine K.;Greenwood, Tiffany A.;Grice, Dorothy E.;Gross, Magdalena;Grozeva, Detelina;Guan, Weihua;Gurling, Hugh;De Haan, Lieuwe;Haines, Jonathan L.;Hakonarson, Hakon;Hallmayer, Joachim;Hamilton, Steven P.;Hamshere, Marian L.;Hansen, Thomas F.;Hartmann, Annette M.;Hautzinger, Martin;Heath, Andrew C.;Henders, Anjali K.;Herms, Stefan;Hickie, Ian B.;Hipolito, Maria;Hoefels, Susanne;Holmans, Peter A.;Holsboer, Florian;Hoogendijk, Witte J.;Hottenga, Jouke-Jan;Hultman, Christina M.;Hus, Vanessa;Ingason, Andres;Ising, Marcus;Jamain, Stephane;Jones, Edward G.;Jones, Ian;Jones, Lisa;Tzeng, Jung-Ying;Kaehler, Anna K.;Kahn, Rene S.;Kandaswamy, Radhika;Keller, Matthew C.;Kennedy, James L.;Kenny, Elaine;Kent, Lindsey;Kim, Yunjung;Kirov, George K.;Klauck, Sabine M.;Klei, Lambertus;Knowles, James A.;Kohli, Martin A.;Koller, Daniel L.;Konte, Bettina;Korszun, Ania;Krabbendam, Lydia;Krasucki, Robert;Kuntsi, Jonna;Kwan, Phoenix;Landen, Mikael;Langstrom, Niklas;Lathrop, Mark;Lawrence, Jacob;Lawson, William B.;Leboyer, Marion;Ledbetter, David H.;Lee, Phil H.;Lencz, Todd;Lesch, Klaus-Peter;Levinson, Douglas F.;Lewis, Cathryn M.;Li, Jun;Lichtenstein, Paul;Lieberman, Jeffrey A.;Lin, Dan-Yu;Linszen, Don H.;Liu, Chunyu;Lohoff, Falk W.;Loo, Sandra K.;Lord, Catherine;Lowe, Jennifer K.;Lucae, Susanne;MacIntyre, Donald J.;Madden, Pamela A. F.;Maestrini, Elena;Magnusson, Patrik K. E.;Mahon, Pamela B.;Maier, Wolfgang;Malhotra, Anil K.;Mane, Shrikant M.;Martin, Christa L.;Martin, Nicholas G.;Mattheisen, Manuel;Matthews, Keith;Mattingsdal, Morten;McCarroll, Steven A.;McGhee, Kevin A.;McGough, James J.;McGrath, Patrick J.;McGuffin, Peter;McInnis, Melvin G.;McIntosh, Andrew;McKinney, Rebecca;McLean, Alan W.;McMahon, Francis J.;McMahon, William M.;McQuillin, Andrew;Medeiros, Helena;Medland, Sarah E.;Meier, Sandra;Melle, Ingrid;Meng, Fan;Meyer, Jobst;Middeldorp, Christel M.;Middleton, Lefkos;Milanova, Vihra;Miranda, Ana;Monaco, Anthony P.;Montgomery, Grant W.;Moran, Jennifer L.;Moreno-De-Luca, Daniel;Morken, Gunnar;Morris, Derek W.;Morrow, Eric M.;Moskvina, Valentina;Muglia, Pierandrea;Muehleisen, Thomas W.;Muir, Walter J.;Mueller-Myhsok, Bertram;Murtha, Michael;Myers, Richard M.;Myin-Germeys, Inez;Neale, Michael C.;Nelson, Stan F.;Nievergelt, Caroline M.;Nikolov, Ivan;Nimgaonkar, Vishwajit;Nolen, Willem A.;Noethen, Markus M.;Nurnberger, John I.;Nwulia, Evaristus A.;Nyholt, Dale R.;O'Dushlaine, Colm;Oades, Robert D.;Olincy, Ann;Oliveira, Guiomar;Olsen, Line;Ophoff, Roel A.;Osby, Urban;Owen, Michael J.;Palotie, Aarno;Parr, Jeremy R.;Paterson, Andrew D.;Pato, Carlos N.;Pato, Michele T.;Penninx, Brenda W.;Pergadia, Michele L.;Pericak-Vance, Margaret A.;Pickard, Benjamin S.;Pimm, Jonathan;Piven, Joseph;Posthuma, Danielle;Potash, James B.;Poustka, Fritz;Propping, Peter;Puri, Vinay;Quested, Digby J.;Quinn, Emma M.;Antoni Ramos-Quiroga, Josep;Rasmussen, Henrik B.;Raychaudhuri, Soumya;Rehnstroem, Karola;Reif, Andreas;Ribases, Marta;Rice, John P.;Rietschel, Marcella;Roeder, Kathryn;Roeyers, Herbert;Rossin, Lizzy;Rothenberger, Aribert;Rouleau, Guy;Ruderfer, Douglas;Rujescu, Dan;Sanders, Alan R.;Sanders, Stephan J.;Santangelo, Susan L.;Sergeant, Joseph A.;Schachar, Russell;Schalling, Martin;Schatzberg, Alan F.;Scheftner, William A.;Schellenberg, Gerard D.;Scherer, Stephen W.;Schork, Nicholas J.;Schulze, Thomas G.;Schumacher, Johannes;Schwarz, Markus;Scolnick, Edward;Scott, Laura J.;Shi, Jianxin;Shilling, Paul D.;Shyn, Stanley I.;Silverman, Jeremy M.;Slager, Susan L.;Smalley, Susan L.;Smit, Johannes H.;Smith, Erin N.;Sonuga-Barke, Edmund J. S.;St Clair, David;State, Matthew;Steffens, Michael;Steinhausen, Hans-Christoph;Strauss, John S.;Strohmaier, Jana;Stroup, T. Scott;Sutcliffe, James S.;Szatmari, Peter;Szelinger, Szabocls;Thirumalai, Srinivasa;Thompson, Robert C.;Todorov, Alexandre A.;Tozzi, Federica;Treutlein, Jens;Uhr, Manfred;van den Oord, Edwin J. C. G.;Van Grootheest, Gerard;Van Os, Jim;Vicente, Astrid M.;Vieland, Veronica J.;Vincent, John B.;Visscher, Peter M.;Walsh, Christopher A.;Wassink, Thomas H.;Watson, Stanley J.;Weissman, Myrna M.;Werge, Thomas;Wienker, Thomas F.;Wijsman, Ellen M.;Willemsen, Gonneke;Williams, Nigel;Willsey, A. Jeremy;Witt, Stephanie H.;Xu, Wei;Young, Allan H.;Yu, Timothy W.;Zammit, Stanley;Zandi, Peter P.;Zhang, Peng;Zitman, Frans G.;Zoellner, Sebastian;Devlin, Bernie;Kelsoe, John R.;Sklar, Pamela;Daly, Mark J.;O'Donovan, Michael C.;Craddock, Nicholas;Sullivan, Patrick F.;Smoller, Jordan W.;Kendler, Kenneth S.;Wray, Naomi R.
通讯作者:
Wray, Naomi R.
影响因子:
4.8
作者:
Dalby, B;Cates, S;Ciccarone, VC
通讯作者:
Ciccarone, VC
影响因子:
2
作者:
Cesarini, Laura;Alfieri, Paolo;Zampino, Giuseppe
通讯作者:
Zampino, Giuseppe
DOI:
10.1002/ajmg.a.33391
发表时间:
2010-05
期刊:
American journal of medical genetics. Part A
影响因子:
--
作者:
Gripp KW;Hopkins E;Doyle D;Dobyns WB
通讯作者:
Dobyns WB
影响因子:
30.8
作者:
Goyal Y;Jindal GA;Pelliccia JL;Yamaya K;Yeung E;Futran AS;Burdine RD;Schüpbach T;Shvartsman SY
通讯作者:
Shvartsman SY