Derivation of human midbrain-specific organoids from neuroepithelial Stem Cells
Anna S. Monzel,Lisa M. Smits,Kathrin Hemmer,Siham Hachi,Edinson Lucumi Moreno,Thea van Wuellen,Javier Jarazo,Jonas Walter,Inga Brüggemann,Ibrahim Boussaad,Emanuel Berger,Ronan M. T. Fleming,Silvia Bolognin,Jens Christian Schwamborn +13 more
Reads0
Chats0
TLDR
A robust human brain organoid system that is highly specific to the midbrain derived from regionally patterned neuroepithelial stem cells is described, which has the potential to be used for advanced in vitro disease modeling and therapy development.Abstract:
Research on human brain development and neurological diseases is limited by the lack of advanced experimental in vitro models that truly recapitulate the complexity of the human brain. Here, we describe a robust human brain organoid system that is highly specific to the midbrain derived from regionally patterned neuroepithelial stem cells. These human midbrain organoids contain spatially organized groups of dopaminergic neurons, which make them an attractive model for the study of Parkinson’s disease. Midbrain organoids are characterized in detail for neuronal, astroglial, and oligodendrocyte differentiation. Furthermore, we show the presence of synaptic connections and electrophysiological activity. The complexity of this model is further highlighted by the myelination of neurites. The present midbrain organoid system has the potential to be used for advanced in vitro disease modeling and therapy development.read more
Citations
More filters
Journal ArticleDOI
The use of brain organoids to investigate neural development and disease
TL;DR: Recent advances in stem cell technologies that enable the generation of human brain organoids from pluripotent stem cells (PSCs) promise to profoundly change understanding of the development of the human brain and enable a detailed study of the pathogenesis of inherited and acquired brain diseases.
Journal ArticleDOI
Brain organoids: advances, applications and challenges.
TL;DR: Recent advances in the development of brain organoid methodologies are summarized and their potential applications as model systems for understanding disease states as well as normal brain development across species are highlighted.
Journal ArticleDOI
New insights into the complex role of mitochondria in Parkinson's disease.
TL;DR: An overview of the literature published in the last three decades on the significance of mitochondria in the pathogenesis of Parkinson's disease is given and the contribution of mitochondrial genome alterations and PD-associated genes to mitochondrial maintenance is described.
Journal ArticleDOI
Induction of myelinating oligodendrocytes in human cortical spheroids
Mayur Madhavan,Zachary S. Nevin,H. Elizabeth Shick,Eric Garrison,Cheryl Clarkson-Paredes,Molly Karl,Benjamin L.L. Clayton,Daniel C. Factor,Kevin C. Allan,Lilianne Barbar,Tanya Jain,Panagiotis Douvaras,Valentina Fossati,Robert H. Miller,Paul J. Tesar +14 more
TL;DR: A method for generating cortical spheroids from human pluripotent stem cells produces maturing oligodendrocytes that can myelinate axons and model myelin disease and drug effects and provides a versatile platform for studies of myelination of the developing central nervous system.
Journal ArticleDOI
Modeling Parkinson’s disease in midbrain-like organoids
Lisa M. Smits,Lydia Reinhardt,Lydia Reinhardt,Peter Reinhardt,Peter Reinhardt,Michael Glatza,Michael Glatza,Anna S. Monzel,Nancy Stanslowsky,Marcelo D. Rosato-Siri,Alessandra Zanon,Paul Antony,Jessica Bellmann,Sarah Nicklas,Kathrin Hemmer,Xiaobing Qing,Emanuel Berger,Norman Kalmbach,Marc Ehrlich,Silvia Bolognin,Andrew A. Hicks,Florian Wegner,Jared Sterneckert,Jared Sterneckert,Jens Christian Schwamborn +24 more
TL;DR: It is demonstrated that three-dimensional differentiation of expandable midbrain floor plate neural progenitor cells (mfNPCs) leads to organoids that resemble key features of the human midbrain that investigate PD-relevant patho-mechanisms.
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
Matrix elasticity directs stem cell lineage specification.
TL;DR: Naive mesenchymal stem cells are shown here to specify lineage and commit to phenotypes with extreme sensitivity to tissue-level elasticity, consistent with the elasticity-insensitive commitment of differentiated cell types.
Journal ArticleDOI
Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells
Junying Yu,Maxim A. Vodyanik,Kim Smuga-Otto,Jessica Antosiewicz-Bourget,Jennifer L. Frane,Shulan Tian,Jeff Nie,Gudrun A. Jonsdottir,Victor Ruotti,Ron Stewart,Igor I. Slukvin,James A. Thomson +11 more
TL;DR: This article showed that OCT4, SOX2, NANOG, and LIN28 factors are sufficient to reprogram human somatic cells to pluripotent stem cells that exhibit the essential characteristics of embryonic stem (ES) cells.
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
Cell shape, cytoskeletal tension, and rhoa regulate stem cell lineage commitment
TL;DR: It is demonstrated that cell shape regulates commitment of human mesenchymal stem cells to adipocyte or osteoblast fate and mechanical cues experienced in developmental and adult contexts, embodied by cell shape, cytoskeletal tension, and RhoA signaling, are integral to the commitment of stem cell fate.
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