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
Engineering three-dimensional microenvironments towards in vitro disease models of the central nervous system.
Lara Yildirimer,Qiang Zhang,Shifeng Kuang,Chung Wai James Cheung,Kyle Alexander Chu,Yong He,Mo Yang,Xin Zhao +7 more
TL;DR: This review mainly focuses on the most recent advances in tissue engineering techniques such as microfluidics, organs-on-a-chip and stem cell technology and recent models aiming to elucidate the underlying pathophysiology of CNS diseases.
Journal ArticleDOI
The moral status of cerebral organoids.
Sorin Hostiuc,Mugurel Constantin Rusu,Ionuţ Negoi,Paula Perlea,Bogdan Dorobanţu,Eduard Drima +5 more
TL;DR: The moral status of cerebral organoids is evaluated and under which conditions their use should be allowed from a bioethical standpoint and practical recommendations for researchers working in this biological field are made.
Journal ArticleDOI
Functional maturation of human neural stem cells in a 3D bioengineered brain model enriched with fetal brain-derived matrix.
Disha Sood,Dana M. Cairns,Jayanth M. Dabbi,Charu Ramakrishnan,Karl Deisseroth,Lauren D. Black,Sabato Santaniello,David L. Kaplan +7 more
TL;DR: Enhanced functional differentiation of human induced neural stem cells into healthy neurons and astrocytes is demonstrated and native biochemical cues in decellularized ECM are identified with notable comparisons between fetal and adult brain-derived ECMs.
Journal ArticleDOI
Pathophysiology and Mechanisms of Zika Virus Infection in the Nervous System.
TL;DR: Although a great deal has been discovered about the genome and pathogenesis of this reemergent flavivirus since this recent outbreak, there still has much more to learn, including the nature of the virus-host interactions and mechanisms that determine its tropism and pathogenicity in the nervous system.
Journal ArticleDOI
Human Induced Pluripotent Stem Cell-Derived 3D-Neurospheres Are Suitable for Neurotoxicity Screening
Julianna Kobolák,Annamária Téglási,Tamás Bellák,Zofia Janstova,Kinga Molnár,Melinda Zana,István Bock,Lajos László,A. Dinnyes,A. Dinnyes +9 more
TL;DR: In this article, a HiPSC-based 3D in vitro system suitable to test neurotoxicity (NT) was presented, where human iPSCs-derived 3D neurospheres grown in 96-well plate format were characterized timewise for 6-weeks.
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