Present and future of modeling human brain development in 3D organoids

被引:73
作者
Quadrato, Giorgia [1 ,2 ]
Arlotta, Paola [1 ,2 ]
机构
[1] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA
[2] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA
关键词
PLURIPOTENT STEM-CELLS; CEREBRAL ORGANOIDS; SELF-ORGANIZATION; HUMAN ES; ALZHEIMERS-DISEASE; HUMAN NEOCORTEX; RADIAL GLIA; CULTURE; PROGENITORS; CDK5RAP2;
D O I
10.1016/j.ceb.2017.11.010
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Three-dimensional (3D) brain organoids derived from human pluripotent stem cells hold great potential to investigate complex human genetic states and to model aspects of human brain development and pathology. However, the field of brain organoids is still in its infancy, and their use has been limited by their variability and their inability to differentiate into 3D structures with reproducible anatomical organization. Here, starting from a review of basic principles of in vitro 'brain organogenesis', we discuss which aspects of human brain development and disease can be faithfully modeled with current brain organoid protocols, and discuss improvements that would allow them to become reliable tools to investigate complex features of human brain development and disease.
引用
收藏
页码:47 / 52
页数:6
相关论文
共 40 条
[1]   Fused cerebral organoids model interactions between brain regions [J].
Bagley, Joshua A. ;
Reumann, Daniel ;
Bian, Shan ;
Levi-Strauss, Julie ;
Knoblich, Juergen A. .
NATURE METHODS, 2017, 14 (07) :743-+
[2]   CDK5RAP2 Regulates Centriole Engagement and Cohesion in Mice [J].
Barrera, Jose A. ;
Kao, Ling-Rong ;
Hammer, Robert E. ;
Seemann, Joachim ;
Fuchs, Jannon L. ;
Megraw, Timothy L. .
DEVELOPMENTAL CELL, 2010, 18 (06) :913-926
[3]   Human iPSC-Derived Cerebral Organoids Model Cellular Features of Lissencephaly and Reveal Prolonged Mitosis of Outer Radial Glia [J].
Bershteyn, Marina ;
Nowakowski, Tomasz J. ;
Pollen, Alex A. ;
Di Lullo, Elizabeth ;
Nene, Aishwarya ;
Wynshaw-Boris, Anthony ;
Kriegstein, Arnold R. .
CELL STEM CELL, 2017, 20 (04) :435-+
[4]   Assembly of functionally integrated human forebrain spheroids [J].
Birey, Fikri ;
Andersen, Jimena ;
Makinson, Christopher D. ;
Islam, Saiful ;
Wei, Wu ;
Huber, Nina ;
Fan, H. Christina ;
Metzler, Kimberly R. Cordes ;
Panagiotakos, Georgia ;
Thom, Nicholas ;
O'Rourke, Nancy A. ;
Steinmetz, Lars M. ;
Bernstein, Jonathan A. ;
Hallmayer, Joachim ;
Huguenard, John R. ;
Pasca, Sergiu P. .
NATURE, 2017, 545 (7652) :54-+
[5]   A centrosomal mechanism involving CDK5RAP2 and CENPJ controls brain size [J].
Bond, J ;
Roberts, E ;
Springell, K ;
Lizarraga, S ;
Scott, S ;
Higgins, J ;
Hampshire, DJ ;
Morrison, EE ;
Leal, GF ;
Silva, EO ;
Costa, SMR ;
Baralle, D ;
Raponi, M ;
Karbani, G ;
Rashid, Y ;
Jafri, H ;
Bennett, C ;
Corry, P ;
Walsh, CA ;
Woods, CG .
NATURE GENETICS, 2005, 37 (04) :353-355
[6]   Human organomics: a fresh approach to understanding human development using single-cell transcriptomics [J].
Camp, J. Gray ;
Treutlein, Barbara .
DEVELOPMENT, 2017, 144 (09) :1584-1587
[7]   Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling [J].
Chambers, Stuart M. ;
Fasano, Christopher A. ;
Papapetrou, Eirini P. ;
Tomishima, Mark ;
Sadelain, Michel ;
Studer, Lorenz .
NATURE BIOTECHNOLOGY, 2009, 27 (03) :275-280
[8]   A three-dimensional human neural cell culture model of Alzheimer's disease [J].
Choi, Se Hoon ;
Kim, Young Hye ;
Hebisch, Matthias ;
Sliwinski, Christopher ;
Lee, Seungkyu ;
D'Avanzo, Carla ;
Chen, Hechao ;
Hooli, Basavaraj ;
Asselin, Caroline ;
Muffat, Julien ;
Klee, Justin B. ;
Zhang, Can ;
Wainger, Brian J. ;
Peitz, Michael ;
Kovacs, Dora M. ;
Woolf, Clifford J. ;
Wagner, Steven L. ;
Tanzi, Rudolph E. ;
Kim, Doo Yeon .
NATURE, 2014, 515 (7526) :274-U293
[9]   The Brazilian Zika virus strain causes birth defects in experimental models [J].
Cugola, Fernanda R. ;
Fernandes, Isabella R. ;
Russo, Fabiele B. ;
Freitas, Beatriz C. ;
Dias, Joao L. M. ;
Guimaraes, Katia P. ;
Benazzato, Cecilia ;
Almeida, Nathalia ;
Pignatari, Graciela C. ;
Romero, Sarah ;
Polonio, Carolina M. ;
Cunha, Isabela ;
Freitas, Carla L. ;
Brandao, Wesley N. ;
Rossato, Cristiano ;
Andrade, David G. ;
Faria, Daniele de P. ;
Garcez, Alexandre T. ;
Buchpigel, Carlos A. ;
Braconi, Carla T. ;
Mendes, Erica ;
Sall, Amadou A. ;
Zanotto, Paolo M. de A. ;
Peron, Jean Pierre S. ;
Muotri, Alysson R. ;
Beltrao-Braga, Patricia C. B. .
NATURE, 2016, 534 (7606) :267-+
[10]   Zika Virus Depletes Neural Progenitors in Human Cerebral Organoids through Activation of the Innate Immune Receptor TLR3 [J].
Dang, Jason ;
Tiwari, Shashi Kant ;
Lichinchi, Gianluigi ;
Qin, Yue ;
Patil, Veena S. ;
Eroshkin, Alexey M. ;
Rana, Tariq M. .
CELL STEM CELL, 2016, 19 (02) :258-265