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
Reads0
Chats0
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
More filters
Journal ArticleDOI
The promises and challenges of human brain organoids as models of neuropsychiatric disease.
TL;DR: The recent development of 3D brain organoids derived from human pluripotent stem cells offers a promising approach for investigating the phenotypic underpinnings of these highly polygenic disorders.
Journal ArticleDOI
Interspecies organogenesis generates autologous functional islets
Tomoyuki Yamaguchi,Hideyuki Sato,Megumi Kato-Itoh,Teppei Goto,Hiromasa Hara,Makoto Sanbo,Naoaki Mizuno,Toshihiro Kobayashi,Ayaka Yanagida,Ayumi Umino,Yasunori Ota,Sanae Hamanaka,Hideki Masaki,Sheikh Tamir Rashid,Masumi Hirabayashi,Hiromitsu Nakauchi,Hiromitsu Nakauchi +16 more
TL;DR: Evidence is provided for the therapeutic potential of PSC-derived islets generated by blastocyst complementation in a xenogeneic host by generating rat-sized pancreata composed of mouse-PSC-derived cells.
Journal ArticleDOI
Down syndrome and the complexity of genome dosage imbalance
TL;DR: The elucidation of the molecular mechanisms that cause or modify the risk for different Down syndrome phenotypes could lead to the introduction of previously unimaginable therapeutic options.
Journal ArticleDOI
Neural Subtype Specification from Human Pluripotent Stem Cells.
Yunlong Tao,Su-Chun Zhang +1 more
TL;DR: The generation of functionally specialized neural subtypes from hPSCs relies on fundamental developmental principles learned from animal studies and enables production of highly enriched neural types with functional attributes that resemble those in the brain.
Journal ArticleDOI
Generation and assembly of human brain region–specific three-dimensional cultures
TL;DR: This protocol describes how to generate and assemble subdomain-specific forebrain spheroids, also known as brain region–specific organoids, from human pluripotent stem cells (hPSCs), and combines them in vitro to assemble forebrain assembloids that recapitulate the interactions of glutamatergic and GABAergic neurons seen in vivo.
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.
Related Papers (5)
Brain-Region-Specific Organoids Using Mini-bioreactors for Modeling ZIKV Exposure
Xuyu Qian,Ha Nam Nguyen,Mingxi M. Song,Christopher Hadiono,Sarah C. Ogden,Christy Hammack,Bing Yao,Gregory R. Hamersky,Fadi Jacob,Chun Zhong,Ki Jun Yoon,William J. Jeang,Li Lin,Yujing Li,Jai Thakor,Daniel A. Berg,Ce Zhang,Eunchai Kang,Michael Chickering,David W. Nauen,Cheng-Ying Ho,Cheng-Ying Ho,Zhexing Wen,Kimberly M. Christian,Pei Yong Shi,Brady J. Maher,Hao Wu,Peng Jin,Hengli Tang,Hongjun Song,Guo Li Ming +30 more