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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Luminal signalling links cell communication to tissue architecture during organogenesis
Sevi Durdu,Murat Iskar,Céline Revenu,Nicole L. Schieber,Andreas Kunze,Peer Bork,Yannick Schwab,Darren Gilmour +7 more
TL;DR: This work investigates how the process of tissue assembly controls signalling activity during organogenesis in vivo, using the migrating zebrafish lateral line primordium to show that fibroblast growth factor (FGF) activity within the tissue controls the frequency at which it deposits rosette-like mechanosensory organs.
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A radical switch in clonality reveals a stem cell niche in the epiphyseal growth plate
Phillip T Newton,Phillip T Newton,Lei Li,Baoyi Zhou,Christoph Schweingruber,Maria Hovorakova,Meng Xie,Xiaoyan Sun,Lakshmi Sandhow,Artem V. Artemov,Artem V. Artemov,E. G. Ivashkin,Simon Suter,Vyacheslav Dyachuk,Vyacheslav Dyachuk,Maha El Shahawy,Amel Gritli-Linde,Thibault Bouderlique,Julian Petersen,Julian Petersen,Annelie Mollbrink,Joakim Lundeberg,Grigori Enikolopov,Hong Qian,Kaj Fried,Maria Kasper,Eva Hedlund,Igor Adameyko,Igor Adameyko,Lars Sävendahl,Andrei S. Chagin,Andrei S. Chagin +31 more
TL;DR: It is demonstrated that, in mice, longitudinal bone growth during fetal and neonatal periods relies on the gradual consumption of chondroprogenitors, whereas in adults, a stem cell niche is formed allowing renewing ofChondro Progenitors and leading to formation of large, stable monoclonal columns of chONDrocytes.
Journal ArticleDOI
Rethinking organoid technology through bioengineering
Elena Garreta,Roger D. Kamm,Susana M. Chuva de Sousa Lopes,Madeline A. Lancaster,Ron Weiss,Xavier Trepat,Insoo Hyun,Insoo Hyun,Nuria Montserrat,Nuria Montserrat +9 more
TL;DR: An overview of bioengineering technologies that can be harnessed to facilitate the culture, self-organization and functionality of human pluripotent stem cell-derived organoids is provided.
Journal ArticleDOI
Small organelle, big responsibility: the role of centrosomes in development and disease
TL;DR: How centrosome dysfunction impacts on complex physiological processes and speculate on the challenges the face when applying knowledge generated from in vitro and in vivo model systems to human development are examined.
Journal ArticleDOI
Cerebral organoids reveal early cortical maldevelopment in schizophrenia-computational anatomy and genomics, role of FGFR1.
Ewa K. Stachowiak,C. A. Benson,Sridhar T. Narla,A. Dimitri,A. Dimitri,L. E. Bayona Chuye,Siddhartha Dhiman,K. Harikrishnan,S. Elahi,D. Freedman,Kristen J. Brennand,Pinaki Sarder,Michal K. Stachowiak +12 more
TL;DR: In this article, the authors used human embryonic stem cells (hESC) and iPSC-derived cerebral organoids from four controls and three schizophrenia patients to model the first trimester of in utero brain development.
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