scholarly journals Control of Outer Radial Glial Stem Cell Mitosis in the Human Brain

Cell Reports ◽  
2014 ◽  
Vol 8 (3) ◽  
pp. 656-664 ◽  
Author(s):  
Bridget E.L. Ostrem ◽  
Jan H. Lui ◽  
Caitlyn C. Gertz ◽  
Arnold R. Kriegstein
Keyword(s):  
Stem Cell ◽  
Human Brain ◽  
Radial Glial ◽  
Cell Mitosis

scholarly journals RBIO-06. IMPLEMENTATION OF HUMAN INDUCED PLURIPOTENT STEM CELL DERIVED CEREBRAL ORGANOIDS TO MODEL NORMAL TISSUE RADIORESPONSE

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii193-ii193
Author(s):  
Lawrence Bronk ◽  
Sanjay Singh ◽  
Riya Thomas ◽  
Luke Parkitny ◽  
Mirjana Maletic-Savatic ◽  
...  
Keyword(s):  
Stem Cell ◽  
Human Brain ◽  
Brain Tissue ◽  
Human Tissue ◽  
Model Systems ◽  
Human Brain Tissue ◽  
Post Irradiation ◽  
Mature Neurons ◽  
Induced Pluripotent ◽  
Effects Of Radiation

Abstract Treatment-related sequelae following cranial irradiation have life changing impacts for patients and their caregivers. Characterization of the basic response of human brain tissue to irradiation has been difficult due to a lack of preclinical models. The direct study of human brain tissue in vitro is becoming possible due to advances in stem cell biology, neuroscience, and tissue engineering with the development of organoids as novel model systems which enable experimentation with human tissue models. We sought to establish a cerebral organoid (CO) model to study the radioresponse of normal human brain tissue. COs were grown using human induced pluripotent stem cells and a modified Lancaster protocol. Compositional analysis during development of the COs showed expected populations of neurons and glia. We confirmed a population of microglia-like cells within the model positive for the makers Iba1 and CD68. After 2-months of maturation, COs were irradiated to 0, 10, and 20 Gy using a Shepard Mark-II Cs-137 irradiator and returned to culture. Subsets of COs were prepared for immunostaining at 30- and 70-days post-irradiation. To examine the effect of irradiation on the neural stem cell (NSC) population, sections were stained for SOX2 and Ki-67 expression denoting NSCs and proliferation respectively. Slides were imaged and scored using the CellProfiler software package. The percentage of proliferating NSCs 30-days post-irradiation was found to be significantly reduced for irradiated COs (5.7% (P=0.007) and 3.4% (P=0.001) for 10 and 20 Gy respectively) compared to control (12.7%). The reduction in the proliferating NSC population subsequently translated to a reduced population of NeuN-labeled mature neurons 70 days post-irradiation. The loss of proliferating NSCs and subsequent reduction in mature neurons demonstrates the long-term effects of radiation. Our initial results indicate COs will be a valuable model to study the effects of radiation therapy on normal and diseased human tissue.

scholarly journals Role of SHH in Patterning Human Pluripotent Cells towards Ventral Forebrain Fates

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 914
Author(s):  
Melanie V. Brady ◽  
Flora M. Vaccarino
Keyword(s):  
Stem Cell ◽  
Human Brain ◽  
Human Development ◽  
Disease Modeling ◽  
Model Systems ◽  
Advantages And Disadvantages ◽  
Technical Ability ◽  
Cellular Phenotypes

The complexities of human neurodevelopment have historically been challenging to decipher but continue to be of great interest in the contexts of healthy neurobiology and disease. The classic animal models and monolayer in vitro systems have limited the types of questions scientists can strive to answer in addition to the technical ability to answer them. However, the tridimensional human stem cell-derived organoid system provides the unique opportunity to model human development and mimic the diverse cellular composition of human organs. This strategy is adaptable and malleable, and these neural organoids possess the morphogenic sensitivity to be patterned in various ways to generate the different regions of the human brain. Furthermore, recapitulating human development provides a platform for disease modeling. One master regulator of human neurodevelopment in many regions of the human brain is sonic hedgehog (SHH), whose expression gradient and pathway activation are responsible for conferring ventral identity and shaping cellular phenotypes throughout the neural axis. This review first discusses the benefits, challenges, and limitations of using organoids for studying human neurodevelopment and disease, comparing advantages and disadvantages with other in vivo and in vitro model systems. Next, we explore the range of control that SHH exhibits on human neurodevelopment, and the application of SHH to various stem cell methodologies, including organoids, to expand our understanding of human development and disease. We outline how this strategy will eventually bring us much closer to uncovering the intricacies of human neurodevelopment and biology.

Embryonic Stem Cell Models of Human Brain Tumors

2018 ◽  
pp. 127-142
Author(s):  
Ludivine Coudière Morrison ◽  
Nazanin Tatari ◽  
Tamra E. Werbowetski-Ogilvie
Keyword(s):  
Stem Cell ◽  
Brain Tumors ◽  
Human Brain ◽  
Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Cell Models ◽  
Human Brain Tumors ◽  
Stem Cell Models

scholarly journals Three-dimensional induced pluripotent stem-cell models of human brain angiogenesis

2020 ◽  
Vol 132 ◽  
pp. 104042 ◽  
Author(s):  
Raleigh M. Linville ◽  
Diego Arevalo ◽  
Joanna C. Maressa ◽  
Nan Zhao ◽  
Peter C. Searson
Keyword(s):  
Stem Cell ◽  
Human Brain ◽  
Pluripotent Stem Cell ◽  
Three Dimensional ◽  
Induced Pluripotent Stem Cell ◽  
Cell Models ◽  
Induced Pluripotent ◽  
Stem Cell Models ◽  
Brain Angiogenesis

scholarly journals 973. Single-cell RNA Sequencing Analysis of Zika Virus Infection in Human Stem Cell-Derived Cerebral Organoids

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S33-S34
Author(s):  
Karen Ocwieja ◽  
Alexandra Stanton ◽  
Alexsia Richards ◽  
Jenna Antonucci ◽  
Travis Hughes ◽  
...  
Keyword(s):  
Stem Cell ◽  
Human Brain ◽  
Single Cell ◽  
Rna Sequencing ◽  
Zika Virus ◽  
Model Systems ◽  
Sequencing Analysis ◽  
Human Stem Cell ◽  
Zikv Infection ◽  
Single Cell Rna Sequencing

Abstract Background The molecular mechanisms underpinning the neurologic and congenital pathologies caused by Zika virus (ZIKV) infection remain poorly understood. One barrier has been the lack of relevant model systems for the developing human brain; however, thanks to advances in the stem cell field, we can now evaluate ZIKV central nervous system infections in human stem cell-derived cerebral organoids which recapitulate complex 3-dimensional neural architecture. Methods We apply Seq-Well—a simple, portable platform for massively parallel single-cell RNA sequencing—to characterize cerebral organoids infected with ZIKV. Using this sequencing method, and published transcriptional profiles, we identify multiple cellular populations in our organoids, including neuroprogenitor cells, intermediate progenitor cells, and terminally differentiated neurons. We detect and quantify host mRNA transcripts and viral RNA with single-cell resolution, defining transcriptional features of uninfected cells and infected cells. Results In this model of the developing brain, we identify preferred tropisms of ZIKV infection and pronounced effects on cell division, differentiation, and death. Our data additionally reveal differences in cellular populations and gene expression within organoids infected by historic and contemporary ZIKV strains from a variety of geographic locations. This finding might help explain phenotypic differences attributed to the viruses, including variable propensity to cause microcephaly. Conclusion Overall, our work provides insight into normal and diseased human brain development, and suggests that both virus replication and host response mechanisms underlie the neuropathology of ZIKV infection. Disclosures All Authors: No reported Disclosures.

scholarly journals Moral Limits of Brain Organoid Research

2019 ◽  
Vol 47 (4) ◽  
pp. 760-767 ◽  
Author(s):  
Julian J. Koplin ◽  
Julian Savulescu
Keyword(s):  
Stem Cell ◽  
Human Brain ◽  
Stem Cell Research ◽  
Cognitive Abilities ◽  
Moral Status ◽  
Ethical Challenges ◽  
Ethical Concerns ◽  
Moral Framework ◽  
Brain Organoid ◽  
Regulations And Guidelines

Brain organoid research raises ethical challenges not seen in other forms of stem cell research. Given that brain organoids partially recapitulate the development of the human brain, it is plausible that brain organoids could one day attain consciousness and perhaps even higher cognitive abilities. Brain organoid research therefore raises difficult questions about these organoids' moral status – questions that currently fall outside the scope of existing regulations and guidelines. This paper shows how these gaps can be addressed. We outline a moral framework for brain organoid research that can address the relevant ethical concerns without unduly impeding this important area of research.

Human brain organoid-on-a-chip to model prenatal nicotine exposure

Lab on a Chip ◽  
2018 ◽  
Vol 18 (6) ◽  
pp. 851-860 ◽  
Author(s):  
Yaqing Wang ◽  
Li Wang ◽  
Yujuan Zhu ◽  
Jianhua Qin
Keyword(s):  
Stem Cell ◽  
Human Brain ◽  
Nicotine Exposure ◽  
Prenatal Nicotine Exposure ◽  
New Strategy ◽  
Organ On A Chip ◽  
Prenatal Nicotine ◽  
Brain Organoid

We present a new strategy to generate stem cell based human brain organoids using an organ-on-a-chip system that allows us to model prenatal nicotine exposure.

scholarly journals Brain tumour stem cells: the undercurrents of human brain cancer and their relationship to neural stem cells

2007 ◽  
Vol 363 (1489) ◽  
pp. 139-152 ◽  
Author(s):  
Peter B Dirks
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Human Brain ◽  
Brain Tumour ◽  
Brain Tumours ◽  
Cell Biology ◽  
Cell Of Origin ◽  
Cellular Targets ◽  
Curative Therapy ◽  
Human Brain Tumours

Conceptual and technical advances in neural stem cell biology are being applied to the study of human brain tumours. These studies suggest that human brain tumours are organized as a hierarchy and are maintained by a small number of tumour cells that have stem cell properties. Most of the bulk population of human brain tumours comprise cells that have lost the ability to initiate and maintain tumour growth. Although the cell of origin for human brain tumours is uncertain, recent evidence points towards the brain's known proliferative zones. The identification of brain tumour stem cells has important implications for understanding brain tumour biology and these cells may be critical cellular targets for curative therapy.

Sign in / Sign up

Export Citation Format

Share Document