New method for controlling neural stem cells brings research closer to brain injury repair

New method for controlling neural stem cells brings research closer to brain injury repair

Nature Communications (2022). DOI: 10.1038 / s41467-022-29839-8 “width =” 800 “height =” 530 “/>
Induction and maintenance of SOX1-positive dorsal neuroepithelial cells. Scheme of neuronal induction of hPSCs in the presence of TGFbR and BMPR inhibitors. After cortical neuronal induction, NES cells express NESTIN in SOX2b-positive cells, SOX1 in TUBB3c-negative cells, and FOXG1d and PAX6e in SOX2-positive cells. The experiment was repeated with 5 biologically independent cell lines. Scalebar:25 μM fSOX1 positive cell ratio in passage 5 cultures of hES (H1, H9, CA1) derived from cNESCs treated with a different set of agents (n = 3 independent cell lines, 10 data points per cell line per group, red bars are Mean ± SEM, one-way ANOVA, Tukey’s test). g Normalized model of cell number changes in cNESCs (data are presented as mean ± SEM for H1-, H9- and CA1-derived cells, n = 3 independent cell lines, 2-way ANOVA, Dunnett’s test) over 10 passages ( 30 days). h Phase contrast image of H1-derived cNESCs (p36) at 4F at day 4 (top) and at day 14 of culture (bottom) forming pink structures. The experiment was repeated with 4 biologically independent cell lines. Scalebar: 50 µm. i: Colony formation examination of cNESCs cultured in 4F before seeding at a density of 200 cells/cm2. Schematic presentation of the components of the target developmental signaling pathway in our assay, protein ligands in bold and chemical inhibitors in italic, and 4F components in red. k Quantification of cell number changes after 96 h of treatment for cNESCs with indicated ligands or chemical inhibitors compared to the 4F condition (n = 3 independent experiments, data are presented as mean ± SEM, ANOVA method, Tukey’s test, white bars are p Nature Communications (2022) DOI: 10.1038 / s41467-022-29839-8

Scientists at the University of Toronto and Sina Health say they have found a new way to control the fate of neural stem cells, bringing researchers one step closer to solving the mystery of how the brain repairs after injury or stroke.

The results were recently published in the journal Nature Communicationsidentified a small group of molecules capable of preventing two major classes of neural stem cells from losing their ability to differentiate into important components of the mammalian cortex, the part of the brain that controls language and information processing.

“This discovery is an exciting extension of platform technologies developed by our laboratory in recent years, which make cellular therapy safe and universal with off-the-shelf products to treat degenerative diseases,” said Andras Nagy, lead author of the study, Professor of Obstetrics and Gynecology at the University of Timerte Medical School, and lead researcher. at the Lunenfeld-Tanenbaum Research Institute at Sinai Health.

GABAergic and glutamatergic neurons are the two major subtypes of neurons in the mammalian forebrain, or cerebral cortex. Both classes develop from cells known as neuroepithelial progenitor cells and play an early and important role in brain development, but then rapidly lose their ability to form other types of cortical cells.

To overcome this limitation, scientists in Nagy’s lab have identified a group of small molecules that are able to maintain the growth of progenitor cells without losing their developmental potential.

Furthermore, when the researchers pulled this mixture of molecules from the stem cells, the cells continued to differentiate into human forebrain cells in large numbers.

said Nagy, who also belongs to the U of T’s Institute of Medical Sciences and holds the Canadian Research Chair in Stem Cells and Regeneration. “These cells could be used in cellular therapies, with the potential to treat strokes and other neurological diseases.”

Understanding the forces that regulate brain development will help identify the underlying causes of diseases, leading to new treatments, said Balazs Varga, first author on the research paper who developed cell-based therapeutic approaches for the project over a decade.

“Our work has identified one way in which we can control the fate of neural stem cells,” said Varga, a former postdoctoral researcher in Nagy’s lab who is now a research associate at the Wellcome Trust for Medical Research, Cambridge Stem Cell Institute. “A better understanding of neuroepithelial cell behavior will provide us with insights into how to control progenitor cell function and brain regeneration.”

Study reveals new clonal relationships in the mouse brain

more information:
Balazs V. Varga et al, Signaling requirements for cortical capacity of transplantable human neuroepithelial stem cells, Nature Communications (2022). DOI: 10.1038 / s41467-022-29839-8

Presented by the University of Toronto

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2022-06-01 14:22:16

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