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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3D Bioprinting Human Induced Pluripotent Stem Cell Constructs for In Situ Cell Proliferation and Successive Multilineage Differentiation
Qi Gu,Qi Gu,Eva Tomaskovic-Crook,Eva Tomaskovic-Crook,Gordon G. Wallace,Jeremy M. Crook,Jeremy M. Crook,Jeremy M. Crook +7 more
TL;DR: This method, employing a clinically amenable polysaccharide‐based bioink, is described as the first example of bioprinting human iPSCs for in situ expansion and sequential differentiation.
Journal ArticleDOI
Evolving Concepts of Gliogenesis: A Look Way Back and Ahead to the Next 25 Years
Marc R. Freeman,David H. Rowitch +1 more
TL;DR: It is proposed that delineating genetic and developmental programs across species will be essential to understand the core functions of glia that allow enhanced neuronal function and to achieve new insights into glial roles in higher-order brain function and neurological disease.
Journal ArticleDOI
Embryoids, organoids and gastruloids: new approaches to understanding embryogenesis.
Mijo Simunovic,Ali H Brivanlou +1 more
TL;DR: The basic physical and biological principles that underlie the self-organization of embryonic stem cells into organoids are discussed, and how this informs human development.
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Cardioids reveal self-organizing principles of human cardiogenesis
Pablo Hofbauer,Stefan M. Jahnel,Nora Papai,Magdalena Giesshammer,Alison Deyett,Clara Schmidt,Mirjam Penc,Katherina Tavernini,Nastasja Grdseloff,Christy Meledeth,Lavinia Ceci Ginistrelli,Claudia Ctortecka,Sejla Salic,Maria Novatchkova,Sasha Mendjan +14 more
TL;DR: In this article, the authors established self-organizing cardioids from human pluripotent stem cells that intrinsically specify, pattern, and morph into chamber-like structures containing a cavity.
Journal ArticleDOI
Modeling of Fibrotic Lung Disease Using 3D Organoids Derived from Human Pluripotent Stem Cells.
Alexandros Strikoudis,Anna Cieślak,Lucas Loffredo,Ya-Wen Chen,Nina Patel,Anjali Saqi,David J. Lederer,Hans-Willem Snoeck +7 more
TL;DR: It is shown that the introduction of all HPS mutations associated with HPSIP promotes fibrotic changes in lung organoids, while the deletion of HPS8 does not, suggesting IL-11 as a therapeutic target.
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