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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Pluripotent Stem-Cell Platforms for Drug Discovery
Kevin G. Chen,Barbara S. Mallon,Kye-Yoon Park,Pamela Gehron Robey,Ronald D.G. McKay,Michael M. Gottesman,Wei Zheng +6 more
TL;DR: This review dissects representative h PDD systems via analysis of hPSC-based 2D-monolayers, 3D culture, and organoids and discusses mechanisms of drug discovery and drug repurposing, and roles of membrane drug transporters in tissue maturation and hPDD.
Journal ArticleDOI
Brain organoid formation on decellularized porcine brain ECM hydrogels
Robin Simsa,Robin Simsa,Theresa S.P. Rothenbücher,Hakan Gürbüz,Nidal Ghosheh,Jenny Emnéus,Lachmi Jenndahl,David L. Kaplan,Niklas Bergh,Alberto Martínez Serrano,Per Fogelstrand +10 more
TL;DR: In this paper, a decellularized adult porcine brain extracellular matrix (B-ECM) was processed into a hydrogel to be used as a scaffold for human embryonic stem cell (hESC)-derived brain organoids.
Journal ArticleDOI
Atypical Neurogenesis in Induced Pluripotent Stem Cells From Autistic Individuals.
Dwaipayan Adhya,Vivek Swarup,Roland Nagy,Lucia Dutan,Carole Shum,Eva P. Valencia-Alarcón,Kamila M. Jozwik,Maria Andreina Mendez,Jamie Horder,Eva Loth,Paulina Nowosiad,Irene Lee,David Skuse,Frances Flinter,Declan G. Murphy,Grainne M. McAlonan,Daniel H. Geschwind,Jack Price,Jason S. Carroll,Deepak Srivastava,Simon Baron-Cohen +20 more
TL;DR: It is indicated that autism-iPSCs diverge from control- iPSCs at a cellular level during early stage of neurodevelopment, which suggests that unique developmental differences associated with autism may be established at early prenatal stages.
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Microporous scaffolds support assembly and differentiation of pancreatic progenitors into β-cell clusters.
TL;DR: The microporous scaffold culture provides a conducive environment that drives in vitro differentiation of hPSC-derived insulin-producing glucose-responsive β-cells and demonstrates the feasibility of these scaffolds as a biomanufacturing platform.
Journal ArticleDOI
The pathogenesis of microcephaly resulting from congenital infections: why is my baby’s head so small?
TL;DR: This review integrates all the findings to create a unified hypothesis of the pathogenesis of congenital microcephaly induced by these infectious agents, cytomegalovirus, rubella virus, and Toxoplasma gondii.
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