Cerebral organoids model human brain development and microcephaly
Madeline A. Lancaster,Magdalena Renner,Carol Anne Martin,Daniel Wenzel,Louise S. Bicknell,Matthew E. Hurles,Tessa Homfray,Josef M. Penninger,Andrew P. Jackson,Juergen A. Knoblich +9 more
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TLDR
A human pluripotent stem cell-derived three-dimensional organoid culture system that develops various discrete, although interdependent, brain regions that include a cerebral cortex containing progenitor populations that organize and produce mature cortical neuron subtypes is developed.Abstract:
The complexity of the human brain has made it difficult to study many brain disorders in model organisms, highlighting the need for an in vitro model of human brain development Here we have developed a human pluripotent stem cell-derived three-dimensional organoid culture system, termed cerebral organoids, that develop various discrete, although interdependent, brain regions These include a cerebral cortex containing progenitor populations that organize and produce mature cortical neuron subtypes Furthermore, cerebral organoids are shown to recapitulate features of human cortical development, namely characteristic progenitor zone organization with abundant outer radial glial stem cells Finally, we use RNA interference and patient-specific induced pluripotent stem cells to model microcephaly, a disorder that has been difficult to recapitulate in mice We demonstrate premature neuronal differentiation in patient organoids, a defect that could help to explain the disease phenotype Together, these data show that three-dimensional organoids can recapitulate development and disease even in this most complex human tissueread more
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hESC-Derived Thalamic Organoids Form Reciprocal Projections When Fused with Cortical Organoids
Yangfei Xiang,Yoshiaki Tanaka,Bilal Cakir,Benjamin Patterson,Kun-Yong Kim,Pingnan Sun,Young-Jin Kang,Mei Zhong,Xinran Liu,Prabir Patra,Sang-Hun Lee,Sherman M. Weissman,In-Hyun Park +12 more
TL;DR: A method to differentiate human embryonic stem cells (hESCs) to thalamic organoids (hThOs) that specifically recapitulate the development of thalamus is described, which provides a platform for understanding humanThalamic development and modeling circuit organizations and related disorders in the brain.
Journal ArticleDOI
High-resolution 3D imaging of fixed and cleared organoids
Johanna F. Dekkers,Maria Alieva,Lianne M Wellens,Hendrikus C R Ariese,Paul R. Jamieson,Annelotte M. Vonk,Gimano D. Amatngalim,Huili Hu,Koen C. Oost,Hugo J. Snippert,Jeffrey M. Beekman,Ellen J. Wehrens,Jane E. Visvader,Jane E. Visvader,Hans Clevers,Anne C. Rios +15 more
TL;DR: A detailed protocol for performing high-resolution 3D imaging of entire organoids harboring fluorescence reporters and following immunolabeling is provided, applicable to a wide range of organoids of differing origins and of various sizes and shapes.
Journal ArticleDOI
Colonic organoids derived from human induced pluripotent stem cells for modeling colorectal cancer and drug testing
Miguel Crespo,Eduardo Vilar,Su-Yi Tsai,Kyle Chang,Sadaf Amin,Tara Srinivasan,Tuo Zhang,Nina H. Pipalia,Huanhuan Joyce Chen,Mavee Witherspoon,Miriam Gordillo,Jenny Xiang,Frederick R. Maxfield,Steven M. Lipkin,Todd Evans,Shuibing Chen +15 more
TL;DR: In this paper, an effective protocol for deriving colonic organoids (COs) from differentiated human embryonic stem cells (hESCs) or induced pluripotent stem cells(iPSCs) was developed for modeling human disease of the large intestine.
Journal ArticleDOI
Genetically engineered cerebral organoids model brain tumor formation.
Shan Bian,Marko Repic,Zhenming Guo,Zhenming Guo,Anoop Kavirayani,Thomas R Burkard,Thomas R Burkard,Joshua A. Bagley,Christian Krauditsch,Jürgen A. Knoblich +9 more
TL;DR: A 3D in vitro model called a neoplastic cerebral organoid (neoCOR), in which brain tumorigenesis is recapitulate by introducing oncogenic mutations in cerebral organoids via transposon- and CRISPR–Cas9-mediated mutagenesis, that will provide a valuable complement to the current basic and preclinical models used to study brain tumor biology.
Journal ArticleDOI
How to make a midbrain dopaminergic neuron
TL;DR: This Primer summarises recent efforts to generate human midbrain dopaminergic neurons in vitro, from pluripotent stem cells or from somatic cells via direct reprogramming.
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