Trace elements during primordial plexiform network formation in human cerebral organoids

Systematic studies of micronutrients during brain formation are hindered by restrictions to animal models and adult post-mortem tissues. Recently, advances in stem cell biology have enabled recapitulation of the early stages of human telencephalon development. In the present work, we exposed cerebral organoids derived from human pluripotent stem cells to synchrotron radiation in order to measure how biologically valuable micronutrients are incorporated and distributed in the exogenously developing brain. Our findings indicate that elemental inclusion in organoids is consistent with human brain tissue and involves calcium, iron, phosphorus, potassium, sulfur, and zinc. Local trends in concentrations suggest a switch from passive to actively mediated transport across cell membranes. Finally, correlational analysis for pairs of elements shows spatially conserved patterns, suggesting they may physically associate, be stored in similar compartments or used in related biological processes. These findings might reflect which trace elements are important during human brain development and will support studies aimed to unravel the consequences of disrupted metal homeostasis for neurodevelopmental diseases, including those manifested in adulthood.

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Trace elements during primordial plexiform network formation in human cerebral organoids

PeerJ ◽

10.7717/peerj.2927 ◽

2017 ◽

Vol 5 ◽

pp. e2927 ◽

Cited By ~ 7

Author(s):

Rafaela C. Sartore ◽

Simone C. Cardoso ◽

Yury V.M. Lages ◽

Julia M. Paraguassu ◽

Mariana P. Stelling ◽

...

Keyword(s):

Trace Elements ◽

Human Brain ◽

Cell Biology ◽

Network Formation ◽

Interaction Patterns ◽

Human Brain Tissue ◽

Concentration Gradients ◽

Human Telencephalon

Systematic studies of micronutrients during brain formation are hindered by restrictions to animal models and adult post-mortem tissues. Recently, advances in stem cell biology have enabled recapitulation of the early stages of human telencephalon developmentin vitro. In the present work, we analyzed cerebral organoids derived from human pluripotent stem cells by synchrotron radiation X-ray fluorescence in order to measure biologically valuable micronutrients incorporated and distributed into the exogenously developing brain. Our findings indicate that elemental inclusion in organoids is consistent with human brain tissue and involves P, S, K, Ca, Fe and Zn. Occurrence of different concentration gradients also suggests active regulation of elemental transmembrane transport. Finally, the analysis of pairs of elements shows interesting elemental interaction patterns that change from 30 to 45 days of development, suggesting short- or long-term associations, such as storage in similar compartments or relevance for time-dependent biological processes. These findings shed light on which trace elements are important during human brain development and will support studies aimed to unravel the consequences of disrupted metal homeostasis for neurodevelopmental diseases, including those manifested in adulthood.

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The Age of Brain Organoids: Tailoring Cell Identity and Functionality for Normal Brain Development and Disease Modeling

Frontiers in Neuroscience ◽

10.3389/fnins.2021.674563 ◽

2021 ◽

Vol 15 ◽

Author(s):

Lisiane O. Porciúncula ◽

Livia Goto-Silva ◽

Pitia F. Ledur ◽

Stevens K. Rehen

Keyword(s):

Human Brain ◽

Brain Development ◽

Functional Activity ◽

Network Formation ◽

Disease Modeling ◽

Morphological Data ◽

Neural Cells ◽

Normal Brain ◽

Human Brain Tissue ◽

Cell Repertoire

Over the past years, brain development has been investigated in rodent models, which were particularly relevant to establish the role of specific genes in this process. However, the cytoarchitectonic features, which determine neuronal network formation complexity, are unique to humans. This implies that the developmental program of the human brain and neurological disorders can only partly be reproduced in rodents. Advancement in the study of the human brain surged with cultures of human brain tissue in the lab, generated from induced pluripotent cells reprogrammed from human somatic tissue. These cultures, termed brain organoids, offer an invaluable model for the study of the human brain. Brain organoids reproduce the cytoarchitecture of the cortex and can develop multiple brain regions and cell types. Integration of functional activity of neural cells within brain organoids with genetic, cellular, and morphological data in a comprehensive model for human development and disease is key to advance in the field. Because the functional activity of neural cells within brain organoids relies on cell repertoire and time in culture, here, we review data supporting the gradual formation of complex neural networks in light of cell maturity within brain organoids. In this context, we discuss how the technology behind brain organoids brought advances in understanding neurodevelopmental, pathogen-induced, and neurodegenerative diseases.

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Organoids: the third dimension of human brain development and disease

The International Journal of Developmental Biology ◽

10.1387/ijdb.210158gk ◽

2021 ◽

Author(s):

Georgia Kouroupi ◽

Kanella Prodromidou ◽

Florentia Papastefanaki ◽

Era Taoufik ◽

Rebecca Matsas

Keyword(s):

Stem Cells ◽

Human Brain ◽

Brain Development ◽

Cell Biology ◽

Embryonic Stem ◽

Two Dimensional ◽

The Third ◽

Human Brain Development ◽

Third Dimension

Stem cell technologies have opened up new avenues in the study of human biology and disease. Especially, the advent of human embryonic stem cells followed by reprograming technologies for generation of induced pluripotent stem cells have instigated studies for modeling human brain development and disease by providing a means to simulate a human tissue with otherwise limited or no accessibility to researchers. Brain development is a complex process achieved in a remarkably controlled spatial and temporal manner through coordinated cellular and molecular events. In vitro models aim to mimic these processes and recapitulate brain organogenesis. Initially, two-dimensional neural cultures presented an innovative landmark for investigating human neuronal and, more recently, glial biology as well as for modeling brain neurodevelopmental and neurodegenerative diseases. The establishment of three-dimensional cultures in the form of brain organoids was an equally important milestone in the field. Brain organoids mimic more closely the in vivo tissue composition and architecture and are more physiologically relevant than monolayer cultures. They therefore represent a more realistic cellular environment for modeling the cell biology and pathology of the nervous system. Here we highlight the journey to recapitulate human brain development and disease in-a-dish, starting from two-dimensional in vitro systems up to the third dimension provided by brain organoids. We discuss the potential of these approaches for modeling human brain development and evolution and their promise for understanding and treating brain disease.

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Human Brain Development: Nature and Nurture

PsycEXTRA Dataset ◽

10.1037/e598612007-001 ◽

2006 ◽

Author(s):

Keyword(s):

Human Brain ◽

Brain Development ◽

Human Brain Development ◽

Nature And Nurture

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Magnetoencephalography: an emerging neuroimaging tool for studying normal and abnormal human brain development

10.3389/978-2-88919-658-6 ◽

2015 ◽

Keyword(s):

Human Brain ◽

Brain Development ◽

Human Brain Development

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Faculty Opinions recommendation of Cerebral organoids model human brain development and microcephaly.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718095215.793483250 ◽

2013 ◽

Author(s):

Elizabeth Cropper ◽

Hongyan Zou

Keyword(s):

Human Brain ◽

Brain Development ◽

Human Brain Development

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Molecular regulation of Snai2 in development and disease

Journal of Cell Science ◽

10.1242/jcs.235127 ◽

2019 ◽

Vol 132 (23) ◽

Author(s):

Wenhui Zhou ◽

Kayla M. Gross ◽

Charlotte Kuperwasser

Keyword(s):

Transcription Factor ◽

Cell Biology ◽

Molecular Mechanisms ◽

Epithelial To Mesenchymal Transition ◽

Zinc Finger Protein ◽

Main Role ◽

Biological Processes ◽

Developmental Defects ◽

Mesenchymal Transition ◽

Damage Repair

ABSTRACT The transcription factor Snai2, encoded by the SNAI2 gene, is an evolutionarily conserved C2H2 zinc finger protein that orchestrates biological processes critical to tissue development and tumorigenesis. Initially characterized as a prototypical epithelial-to-mesenchymal transition (EMT) transcription factor, Snai2 has been shown more recently to participate in a wider variety of biological processes, including tumor metastasis, stem and/or progenitor cell biology, cellular differentiation, vascular remodeling and DNA damage repair. The main role of Snai2 in controlling such processes involves facilitating the epigenetic regulation of transcriptional programs, and, as such, its dysregulation manifests in developmental defects, disruption of tissue homeostasis, and other disease conditions. Here, we discuss our current understanding of the molecular mechanisms regulating Snai2 expression, abundance and activity. In addition, we outline how these mechanisms contribute to disease phenotypes or how they may impact rational therapeutic targeting of Snai2 dysregulation in human disease.

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