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
Growth of human breast tissues from patient cells in 3D hydrogel scaffolds
TL;DR: These 3D hydrogel scaffolds support the growth of complex mammary tissues from primary patient-derived cells and are anticipate that this culture system will empower future studies of human mammary gland development and biology.
Journal ArticleDOI
Evaluation of steroidomics by liquid chromatography hyphenated to mass spectrometry as a powerful analytical strategy for measuring human steroid perturbations
Fabienne Jeanneret,David Tonoli,David Tonoli,Michel F. Rossier,Martial Saugy,Julien Boccard,Serge Rudaz +6 more
TL;DR: This review presents the evolution of steroid analytical techniques, including gas chromatography coupled to mass spectrometry (GC-MS), immunoassay (IA) and targeted liquid chromatography (LC-MS) and it evaluates the potential of extended steroid profiles by a metabolomics-based approach, namely steroidomics.
Journal ArticleDOI
Chasing the Paradigm: Clinical Translation of 25 Years of Tissue Engineering.
TL;DR: Based on their success and other significant research accomplishments, platforms of innovation were identified and will enable tissue engineering inspired therapies to meet the requirements necessary for large-scale manufacturing and Food and Drug Administration approval for a diverse range of indications.
Journal ArticleDOI
Creating Patient-Specific Neural Cells for the In Vitro Study of Brain Disorders
Kristen J. Brennand,M. Carol Marchetto,Nissim Benvenisty,Oliver Brüstle,Allison D. Ebert,Juan Carlos Izpisua Belmonte,Ajamete Kaykas,Madeline A. Lancaster,Frederick J. Livesey,Michael J. McConnell,Ronald D.G. McKay,Eric M. Morrow,Alysson R. Muotri,David M. Panchision,Lee L. Rubin,Akira Sawa,Frank Soldner,Hongjun Song,Lorenz Studer,Sally Temple,Flora M. Vaccarino,Jun Wu,Pierre Vanderhaeghen,Fred H. Gage,Rudolf Jaenisch +24 more
TL;DR: This opinion piece outlines the collective views on the current state of hiPSC-based disease modeling and discusses what the field sees to be the critical objectives that must be addressed collectively as a field.
Journal ArticleDOI
Editing the genome of hiPSC with CRISPR/Cas9: disease models
TL;DR: Analysis of isogenic cell pairs that differ in a single genetic change allows a thorough assessment of the molecular and cellular phenotypes that result from this abnormality, and establishes the true causative lesion.
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