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
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
Citations
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Journal ArticleDOI
An in vivo model of functional and vascularized human brain organoids
Abed AlFatah Mansour,J. Tiago Gonçalves,Cooper W Bloyd,Hao Li,Sarah Fernandes,Sarah Fernandes,Daphne Quang,Stephen T. Johnston,Sarah L. Parylak,Xin Jin,Fred H. Gage +10 more
TL;DR: A method for transplanting human brain organoids into the adult mouse brain is established and progressive neuronal differentiation and maturation, gliogenesis, integration of microglia, and growth of axons to multiple regions of the host brain are shown.
Journal ArticleDOI
Self-organization of axial polarity, inside-out layer pattern, and species-specific progenitor dynamics in human ES cell–derived neocortex
Taisuke Kadoshima,Hideya Sakaguchi,Tokushige Nakano,Mika Soen,Satoshi Ando,Mototsugu Eiraku,Yoshiki Sasai +6 more
TL;DR: New self-organizing aspects of human corticogenesis are shown: spontaneous development of intracortical polarity, curving morphology, and complex zone separations, which suggest human neocorticogenesis involves intrinsic programs that enable the emergence of complex neocortical features.
Journal ArticleDOI
Organoid Models and Applications in Biomedical Research
TL;DR: Historical advances in the field are outlined and some of the major recent developments in 3D human organoid formation are described, underline current limitations and highlight examples of how organoid technology can be applied in biomedical research.
Journal ArticleDOI
Nephron organoids derived from human pluripotent stem cells model kidney development and injury
Ryuji Morizane,Ryuji Morizane,Albert Q. Lam,Albert Q. Lam,Benjamin S. Freedman,Benjamin S. Freedman,Seiji Kishi,Seiji Kishi,M. Todd Valerius,M. Todd Valerius,Joseph V. Bonventre,Joseph V. Bonventre +11 more
TL;DR: An efficient, chemically defined protocol for differentiating hPSCs into multipotent nephrons progenitor cells (NPCs) that can form nephron-like structures that can be used to study mechanisms of human kidney development and toxicity is reported.
Journal ArticleDOI
iPSC-Derived Human Microglia-like Cells to Study Neurological Diseases
Edsel M. Abud,Ricardo Ramirez,Eric S. Martinez,Luke M. Healy,Cecilia H.H. Nguyen,Sean A. Newman,Andriy V. Yeromin,Vanessa M. Scarfone,Samuel E. Marsh,Cristhian Fimbres,Chad A. Caraway,Gianna M. Fote,Abdullah M. Madany,Anshu Agrawal,Rakez Kayed,Karen H. Gylys,Michael D. Cahalan,Brian J. Cummings,Jack P. Antel,Ali Mortazavi,Monica J. Carson,Wayne W. Poon,Mathew Blurton-Jones +22 more
TL;DR: iMGLs were used to examine the effects of Aβ fibrils and brain-derived tau oligomers on AD-related gene expression and to interrogate mechanisms involved in synaptic pruning, and whole-transcriptome analysis demonstrates that they are highly similar to cultured adult and fetal human microglia.
References
More filters
Journal ArticleDOI
Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.
TL;DR: Induction of pluripotent stem cells from mouse embryonic or adult fibroblasts by introducing four factors, Oct3/4, Sox2, c-Myc, and Klf4, under ES cell culture conditions is demonstrated and iPS cells, designated iPS, exhibit the morphology and growth properties of ES cells and express ES cell marker genes.
Journal ArticleDOI
Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche.
Toshiro Sato,Robert G.J. Vries,Hugo J. Snippert,Marc van de Wetering,Nick Barker,Daniel E. Stange,Johan H. van Es,Arie Abo,Pekka Kujala,Peter J. Peters,Hans Clevers +10 more
TL;DR: It is concluded that intestinal cryptvillus units are self-organizing structures, which can be built from a single stem cell in the absence of a non-epithelial cellular niche.
Journal ArticleDOI
Generation of germline-competent induced pluripotent stem cells
TL;DR: iPS cells competent for germline chimaeras can be obtained from fibroblasts, but retroviral introduction of c-Myc should be avoided for clinical application.
Journal ArticleDOI
A ROCK inhibitor permits survival of dissociated human embryonic stem cells
Kiichi Watanabe,Morio Ueno,Daisuke Kamiya,Ayaka Nishiyama,Michiru Matsumura,Takafumi Wataya,Jun Takahashi,Satomi Nishikawa,Shin-Ichi Nishikawa,Keiko Muguruma,Yoshiki Sasai +10 more
TL;DR: Application of a selective Rho-associated kinase (ROCK) inhibitor, Y-27632, to hES cells markedly diminishes dissociation-induced apoptosis, increases cloning efficiency and facilitates subcloning after gene transfer, and enables SFEB-cultured hES Cells to survive and differentiate into Bf1+ cortical and basal telencephalic progenitors.
Journal ArticleDOI
The cell biology of neurogenesis.
TL;DR: In this paper, the authors discuss how these features change during development from neuroepithelial to radial glial cells, and how this transition affects cell fate and neurogenesis.
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