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 cytoskeletal arrangements necessary to neurogenesis.
TL;DR: The importance of iPSC technology to study the processes of cytoskeletal-driven morphological changes during neuronal differentiation is highlighted, which earlier drive the morphology of the neuronal precursors, and later the migrating/mature neurons.
Journal ArticleDOI
Modeling Sporadic Alzheimer's Disease in Human Brain Organoids under Serum Exposure
Xianwei Chen,Guoqiang Sun,E Tian,Mingzi Zhang,Hayk Davtyan,Thomas G. Beach,Eric M. Reiman,Mathew Blurton-Jones,David M. Holtzman,Yanhong Shi +9 more
TL;DR: In this paper, the authors used human induced pluripotent stem cell (hiPSC)-derived 3D brain organoids to model sporadic Alzheimer's disease (sAD) and found that serum exposure increased amyloid beta (Aβ) aggregates and phosphorylated microtubule-associated tau protein (p-Tau) level.
Journal ArticleDOI
Advancing models of neural development with biomaterials.
Julien G Roth,Michelle S. Huang,Thomas L. Li,Vivian R. Feig,Yuanwen Jiang,Bianxiao Cui,Henry T. Greely,Zhenan Bao,Sergiu P. Paşca,Sarah C. Heilshorn +9 more
TL;DR: Heilshorn et al. as discussed by the authors reviewed biomaterial-based approaches that may be integrated into these models in an effort to develop them further and better recapitulate neurodevelopmental processes.
Journal ArticleDOI
Hydrogel-based milliwell arrays for standardized and scalable retinal organoid cultures
Sarah Decembrini,Sarah Decembrini,Sylke Hoehnel,Nathalie Brandenberg,Yvan Arsenijevic,Matthias P. Lutolf +5 more
TL;DR: A tissue-engineering approach to accelerate and standardize the production of retinal organoids by culturing mouse embryonic stem cells (mESC) in optimal physico-chemical microenvironments and should be useful for applications that require scalability and single-organoid traceability.
Journal ArticleDOI
Microfluidic Organoids-on-a-Chip: Quantum Leap in Cancer Research.
TL;DR: Organ-like cell clusters, so-called organoids, have provided a whole new level of bioinspiration for ex vivo systems Microfluidic organoid or organs-on-a-chip platforms are a new group of micro-engineered promising models that recapitulate 3D tissue structure and physiology and combines several advantages of current in vivo and in vitro models as discussed by the authors.
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