Modeling Human Brain Development And Disease In Stem Cell Derived 3D Organoid Culture

2017 ◽  
Vol 27 ◽  
pp. S358
Author(s):  
Jurgen Knoblich
Keyword(s):  
Stem Cell ◽  
Human Brain ◽  
Brain Development ◽  
Organoid Culture ◽  
Human Brain Development

scholarly journals A human stem cell resource to decipher the biochemical and cellular basis of neurodevelopmental defects in Lowe Syndrome

Biology Open ◽  
2022 ◽  
Author(s):  
Bilal M. Akhtar ◽  
Priyanka Bhatia ◽  
Shubhra Acharya ◽  
Sanjeev Sharma ◽  
Yojet Sharma ◽  
...  
Keyword(s):  
Stem Cell ◽  
Lipid Metabolism ◽  
Human Brain ◽  
Brain Development ◽  
Cell Lines ◽  
Brain Function ◽  
Lowe Syndrome ◽  
Human Stem Cell ◽  
Human Brain Development ◽  
Developmental Features

Human brain development is a complex process where multiple cellular and developmental events are co-ordinated to generate normal structure and function. Alteration in any of these events can impact brain development, manifesting clinically as neurodevelopmental disorders. Human genetic disorders of lipid metabolism often present with features of altered brain function. Lowe syndrome (LS), is a X-linked recessive disease with features of altered brain function. LS results from mutations in OCRL1 that encodes a phosphoinositide 5-phosphatase enzyme. However, the cellular mechanisms by which loss of OCRL1 leads to brain defects remain unknown. Human brain development involves several cellular and developmental features not conserved in other species and understanding such mechanisms remains a challenge. Rodent models of LS have been generated, but failed to recapitulate features of the human disease. Here we describe the generation of human stem cell lines from LS patients. Further, we present biochemical characterization of lipid metabolism in patient cell lines and demonstrate their use as a “disease-in-a-dish” model for understanding the mechanism by which loss of OCRL1 leads to altered cellular and physiological brain development.

scholarly journals A human stem cell resource to decipher the biochemical and cellular basis of neurodevelopmental defects in Lowe Syndrome

2021 ◽  
Author(s):  
Bilal Akhtar ◽  
Priyanka Bhatia ◽  
Shubhra Acharya ◽  
Sanjeev Sharma ◽  
Yojet Sharma ◽  
...  
Keyword(s):  
Stem Cell ◽  
Lipid Metabolism ◽  
Human Brain ◽  
Brain Development ◽  
Cell Lines ◽  
Brain Function ◽  
Lowe Syndrome ◽  
Human Stem Cell ◽  
Human Brain Development ◽  
Developmental Features

Human brain development is a complex process where multiple cellular and developmental events are co-ordinated to generate normal structure and function. Alteration in any of these events can impact brain development, manifesting clinically as neurodevelopmental disorders. Human genetic disorders of lipid metabolism often present with features of altered brain function. Lowe syndrome (LS), is a X-linked recessive disease with features of altered brain function. LS results from mutations in OCRL1 that encodes a phosphoinositide 5-phosphatase enzyme. However, the cellular mechanisms by which loss of OCRL1 leads to brain defects remain unknown. Human brain development involves several cellular and developmental features not conserved in other species and understanding such mechanisms remains a challenge. Rodent models of LS have been generated, but failed to recapitulate features of the human disease. Here we describe the generation of human stem cell lines from LS patients. Further, we present biochemical characterization of lipid metabolism in patient cell lines and demonstrate their use as a disease-in-a-dish model for understanding the mechanism by which loss of OCRL1 leads to altered cellular and physiological brain development.

scholarly journals Characterization of the ventricular-subventricular stem cell niche during human brain development

Development ◽  
2018 ◽  
Vol 145 (20) ◽  
pp. dev170100 ◽  
Author(s):  
Amanda M. Coletti ◽  
Deepinder Singh ◽  
Saurabh Kumar ◽  
Tasnuva Nuhat Shafin ◽  
Patrick J. Briody ◽  
...  
Keyword(s):  
Stem Cell ◽  
Human Brain ◽  
Brain Development ◽  
Stem Cell Niche ◽  
Human Brain Development ◽  
Cell Niche

scholarly journals Stem Cell Models of Human Brain Development

2016 ◽  
Vol 18 (6) ◽  
pp. 736-748 ◽  
Author(s):  
Iva Kelava ◽  
Madeline A. Lancaster
Keyword(s):  
Stem Cell ◽  
Human Brain ◽  
Brain Development ◽  
Cell Models ◽  
Human Brain Development ◽  
Stem Cell Models

scholarly journals §Using organoids to study human brain development and evolution

2021 ◽  
Author(s):  
Wai‐Kit Chan ◽  
Rana Fetit ◽  
Rosie Griffiths ◽  
Helen Marshall ◽  
John O Mason ◽  
...  
Keyword(s):  
Human Brain ◽  
Brain Development ◽  
Human Brain Development ◽  
Development And Evolution

scholarly journals Single-cell atlas of early human brain development highlights heterogeneity of human neuroepithelial cells and early radial glia

2021 ◽  
Author(s):  
Ugomma C. Eze ◽  
Aparna Bhaduri ◽  
Maximilian Haeussler ◽  
Tomasz J. Nowakowski ◽  
Arnold R. Kriegstein
Keyword(s):  
Human Brain ◽  
Brain Development ◽  
Single Cell ◽  
Radial Glia ◽  
Cortical Development ◽  
Cell Types ◽  
Human Cortex ◽  
Early Stages ◽  
Human Brain Development ◽  
Neuroepithelial Cells

AbstractThe human cortex comprises diverse cell types that emerge from an initially uniform neuroepithelium that gives rise to radial glia, the neural stem cells of the cortex. To characterize the earliest stages of human brain development, we performed single-cell RNA-sequencing across regions of the developing human brain, including the telencephalon, diencephalon, midbrain, hindbrain and cerebellum. We identify nine progenitor populations physically proximal to the telencephalon, suggesting more heterogeneity than previously described, including a highly prevalent mesenchymal-like population that disappears once neurogenesis begins. Comparison of human and mouse progenitor populations at corresponding stages identifies two progenitor clusters that are enriched in the early stages of human cortical development. We also find that organoid systems display low fidelity to neuroepithelial and early radial glia cell types, but improve as neurogenesis progresses. Overall, we provide a comprehensive molecular and spatial atlas of early stages of human brain and cortical development.

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