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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Brain organoids: an ensemble of bioassays to investigate human neurodevelopment and disease.
TL;DR: Diverse brain organoid techniques offer bioassays to investigate new phenotypes associated with human brain disorders that are difficult to study in monolayer cultures and need to aim at later stages of neurodevelopment, linked with neuronal activity and connections, to unravel further disease-associated phenotypes.
Journal ArticleDOI
A comprehensive library of human transcription factors for cell fate engineering
Alex Hay-Man Ng,Alex Hay-Man Ng,Parastoo Khoshakhlagh,Parastoo Khoshakhlagh,Jesus Eduardo Rojo Arias,Jesus Eduardo Rojo Arias,Giovanni Pasquini,Kai Wang,Kai Wang,Anka Swiersy,Seth L. Shipman,Evan Appleton,Evan Appleton,Kiavash Kiaee,Kiavash Kiaee,Richie E. Kohman,Richie E. Kohman,Andyna Vernet,Matthew Dysart,Matthew Dysart,Kathleen Leeper,Kathleen Leeper,Wren Saylor,Wren Saylor,Jeremy Y. Huang,Jeremy Y. Huang,Amanda R. Graveline,Jussi Taipale,Jussi Taipale,Jussi Taipale,David E. Hill,Marc Vidal,Juan M. Melero-Martin,Juan M. Melero-Martin,Volker Busskamp,Volker Busskamp,George M. Church,George M. Church +37 more
TL;DR: This work screened the library in three hPSC lines and discovered 290 TFs, including 241 previously unreported, that induce differentiation in four days without alteration of external soluble or biomechanical cues, and used four of the hits to program hPSCs into neurons, fibroblasts, oligodendrocytes and vascular endothelial–like cells that have molecular and functional similarity to primary cells.
Modeling psychiatric disorders for developing effective treatments
TL;DR: The utility and limitations of animal models are discussed, and the importance of shifting from behavioral analysis to identifying neurophysiological abnormalities, which are likely to be more conserved across species and thus may increase translatability.
Journal ArticleDOI
Kidney organoids: accurate models or fortunate accidents.
TL;DR: How well human kidney organoids model the human fetal kidney and how the remaining differences challenge their utility are discussed.
Journal ArticleDOI
Kidney micro-organoids in suspension culture as a scalable source of human pluripotent stem cell-derived kidney cells
Santhosh V. Kumar,Pei Xuan Er,Kynan T. Lawlor,Ali Motazedian,Michelle Scurr,Irene M. Ghobrial,Alexander N. Combes,Luke Zappia,Alicia Oshlack,Edouard G. Stanley,Melissa H. Little +10 more
TL;DR: A modified suspension culture method for the generation of kidney micro-organoids from human pluripotent stem cells offers a simple and cost-effective method for expansion of hPSC-derived kidney cells, facilitating scale-up of kidney cell types in vitro for biomedical applications.
References
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