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Organoids are the annual method selected by Nature Methods in 2017.
Cells can be derived from the human body and produce tissue structures similar to organs, which are used as a research model close to the human body for scientific research and drug screening.
Traditional brain organoids The traditional brain organoid culture process is as follows: Induced pluripotent stem cell (iPSC)-derived cells are grown in neural induction medium to produce neuroectoderm, embedded in Matrigel, and grown in a rotating bioreactor or orbital shaker , In order to better spread and obtain three-dimensional brain organs.
When exposed to retinoic acid, brain organs form self-association and organization through self-assembly mode, forming different populations of neural progenitor cells, including radial glial cells, and these neural progenitor cells expand to form the brain structure.
Traditional brain organoid culture (Document 1) Traditional brain organoids have the basic structure and cell types of the brain and can be used for basic scientific research and drug screening.
But they may not have the ability to develop and mature themselves, or simulate complex development, maturation, aging and other processes.
Brain organoids with self-maturation ability recently came from Professor Daniel H.
Geschwind of UCLA and Professor Sergiu P.
Pașca of Stanford University.
They published the latest results in Nature Neuroscience to build a self-developed and mature brain that can be cultivated for a long time.
Cortical organs, in which key genes, proteins, epigenetic changes, etc.
, can basically completely simulate the development of the cerebral cortex from the fetus to the postpartum period.
Research summary Human stem cell-derived models are expected to accelerate our understanding of brain diseases, but it is unknown whether they have the ability to mature beyond the middle and late stages of the fetus, which may limit their utility.
The authors used a direct differentiation protocol to comprehensively assess the degree of in vitro maturity.
Based on genome-wide analysis of the epigenetic clock and transcriptome, as well as RNA editing, it was observed that the three-dimensional human cortical organic matter developed to the postpartum stage between 250 and 300 days, which is a time axis parallel to the development of the body.
The authors describe several known developmental milestones, including switches in the histone deacetylase complex and NMDA receptor subunits, confirming this at the protein and physiological level.
These results indicate that important components of the in vivo development plan still exist in vitro.
Further map neurodevelopmental and neurodegenerative disease risk genes to in vitro gene expression trajectories to provide a resource and network tool (gene expression in cortical organs, GECO) to guide disease modeling.
Main research data 1.
Culture method Compared with the classical method, the author's culture method does not implant the pluripotent stem cell suspension into Matrigel. (As described in the original text: We previously developed a directed method of differentiation of human pluripotent stem cells in suspension that does not involve embedding into matrices.
This approach generates dorsal forebrain organoids named human cortical spheroid (hCS) with high reliability that can be cultured for more than 20 months progressing from neurogenesis to astrogenesis) 2.
Transcriptome and methylation maturation during more than 600 days of culture 3.
Changes in biological and cell type markers during more than 600 days of culture 4.
Process of RNA editing in cortical organs RNA editing is a major RNA processing mechanism that is dynamically regulated during brain development in the body.
RNA editing has been proven to show developmental trajectories that vary with the maturity of the body.
5.
Changes in subtype switches during development 6.
Location of neurodevelopmental and neuropsychiatric disorder genes to hCS differentiation.
Note: ASD: Autism ID: Intellectual hypoplasia SCZ: Schizophrenia 7.
Location of neurodegenerative disease genes Note on hCS differentiation: AD: Alzheimer’s disease PD: Parkinson’s syndrome 360 Comment: Scientists at the University of California and Stanford University have innovatively developed cortical organs that can mature themselves and can simulate the body in vitro using an in vitro model The process of neurodevelopment provides a simulation research tool for studying neurodevelopmental insufficiency, psychiatric disorders, neurodegenerative diseases, etc. Main references Tanya Chhibber et al,CNS organoids: an innovative tool for neurological disease modeling and drug neurotoxicity screening,Drug Discovery Today, November 2019Aaron Gordon et al,Long-term maturation of human cortical organoids matches key early postnatal transitions, Nature Neuroscience volume 24, pages331–342(2021) Description: The copyright belongs to the original author of the article, and Bio360 shares and adds its own opinions.
Cells can be derived from the human body and produce tissue structures similar to organs, which are used as a research model close to the human body for scientific research and drug screening.
Traditional brain organoids The traditional brain organoid culture process is as follows: Induced pluripotent stem cell (iPSC)-derived cells are grown in neural induction medium to produce neuroectoderm, embedded in Matrigel, and grown in a rotating bioreactor or orbital shaker , In order to better spread and obtain three-dimensional brain organs.
When exposed to retinoic acid, brain organs form self-association and organization through self-assembly mode, forming different populations of neural progenitor cells, including radial glial cells, and these neural progenitor cells expand to form the brain structure.
Traditional brain organoid culture (Document 1) Traditional brain organoids have the basic structure and cell types of the brain and can be used for basic scientific research and drug screening.
But they may not have the ability to develop and mature themselves, or simulate complex development, maturation, aging and other processes.
Brain organoids with self-maturation ability recently came from Professor Daniel H.
Geschwind of UCLA and Professor Sergiu P.
Pașca of Stanford University.
They published the latest results in Nature Neuroscience to build a self-developed and mature brain that can be cultivated for a long time.
Cortical organs, in which key genes, proteins, epigenetic changes, etc.
, can basically completely simulate the development of the cerebral cortex from the fetus to the postpartum period.
Research summary Human stem cell-derived models are expected to accelerate our understanding of brain diseases, but it is unknown whether they have the ability to mature beyond the middle and late stages of the fetus, which may limit their utility.
The authors used a direct differentiation protocol to comprehensively assess the degree of in vitro maturity.
Based on genome-wide analysis of the epigenetic clock and transcriptome, as well as RNA editing, it was observed that the three-dimensional human cortical organic matter developed to the postpartum stage between 250 and 300 days, which is a time axis parallel to the development of the body.
The authors describe several known developmental milestones, including switches in the histone deacetylase complex and NMDA receptor subunits, confirming this at the protein and physiological level.
These results indicate that important components of the in vivo development plan still exist in vitro.
Further map neurodevelopmental and neurodegenerative disease risk genes to in vitro gene expression trajectories to provide a resource and network tool (gene expression in cortical organs, GECO) to guide disease modeling.
Main research data 1.
Culture method Compared with the classical method, the author's culture method does not implant the pluripotent stem cell suspension into Matrigel. (As described in the original text: We previously developed a directed method of differentiation of human pluripotent stem cells in suspension that does not involve embedding into matrices.
This approach generates dorsal forebrain organoids named human cortical spheroid (hCS) with high reliability that can be cultured for more than 20 months progressing from neurogenesis to astrogenesis) 2.
Transcriptome and methylation maturation during more than 600 days of culture 3.
Changes in biological and cell type markers during more than 600 days of culture 4.
Process of RNA editing in cortical organs RNA editing is a major RNA processing mechanism that is dynamically regulated during brain development in the body.
RNA editing has been proven to show developmental trajectories that vary with the maturity of the body.
5.
Changes in subtype switches during development 6.
Location of neurodevelopmental and neuropsychiatric disorder genes to hCS differentiation.
Note: ASD: Autism ID: Intellectual hypoplasia SCZ: Schizophrenia 7.
Location of neurodegenerative disease genes Note on hCS differentiation: AD: Alzheimer’s disease PD: Parkinson’s syndrome 360 Comment: Scientists at the University of California and Stanford University have innovatively developed cortical organs that can mature themselves and can simulate the body in vitro using an in vitro model The process of neurodevelopment provides a simulation research tool for studying neurodevelopmental insufficiency, psychiatric disorders, neurodegenerative diseases, etc. Main references Tanya Chhibber et al,CNS organoids: an innovative tool for neurological disease modeling and drug neurotoxicity screening,Drug Discovery Today, November 2019Aaron Gordon et al,Long-term maturation of human cortical organoids matches key early postnatal transitions, Nature Neuroscience volume 24, pages331–342(2021) Description: The copyright belongs to the original author of the article, and Bio360 shares and adds its own opinions.
