Growing Glia: Cultivating Human Stem Cell Models of Gliogenesis in Health and Disease

Lanjewar, Samantha; Sloan, Steven A.

doi:10.3389/fcell.2021.649538

Cited by 20 publications

(20 citation statements)

References 171 publications

(202 reference statements)

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“…During cortical development, neurons are generated first, followed by astrocytes, and then oligodendrocytes (see Sauvageot and Stiles, 2002 ; Lanjewar and Sloan, 2021 for a review). Glial cells make up at least 50% of brain cells ( Rowitch and Kriegstein, 2010 ).…”

Section: Overview Of the Timeline Of Neurogenesis Gliogenesis And Neu...mentioning

confidence: 99%

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The Challenging Pathway of Treatment for Neurogenesis Impairment in Down Syndrome: Achievements and Perspectives

Stagni

Bartesaghi

2022

Front. Cell. Neurosci.

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Down syndrome (DS), also known as trisomy 21, is a genetic disorder caused by triplication of Chromosome 21. Gene triplication may compromise different body functions but invariably impairs intellectual abilities starting from infancy. Moreover, after the fourth decade of life people with DS are likely to develop Alzheimer’s disease. Neurogenesis impairment during fetal life stages and dendritic pathology emerging in early infancy are thought to be key determinants of alterations in brain functioning in DS. Although the progressive improvement in medical care has led to a notable increase in life expectancy for people with DS, there are currently no treatments for intellectual disability. Increasing evidence in mouse models of DS reveals that pharmacological interventions in the embryonic and neonatal periods may greatly benefit brain development and cognitive performance. The most striking results have been obtained with pharmacotherapies during embryonic life stages, indicating that it is possible to pharmacologically rescue the severe neurodevelopmental defects linked to the trisomic condition. These findings provide hope that similar benefits may be possible for people with DS. This review summarizes current knowledge regarding (i) the scope and timeline of neurogenesis (and dendritic) alterations in DS, in order to delineate suitable windows for treatment; (ii) the role of triplicated genes that are most likely to be the key determinants of these alterations, in order to highlight possible therapeutic targets; and (iii) prenatal and neonatal treatments that have proved to be effective in mouse models, in order to rationalize the choice of treatment for human application. Based on this body of evidence we will discuss prospects and challenges for fetal therapy in individuals with DS as a potential means of drastically counteracting the deleterious effects of gene triplication.

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Section: Overview Of the Timeline Of Neurogenesis Gliogenesis And Neu...mentioning

confidence: 99%

“…Microglia cells that, unlike astrocytes and oligodendrocytes are of mesodermal origin ( Rowitch and Kriegstein, 2010 ), invade the brain as early as GW5. Microglial migration and proliferation continue until around GW24 (see Lanjewar and Sloan, 2021 ).…”

Section: Overview Of the Timeline Of Neurogenesis Gliogenesis And Neu...mentioning

confidence: 99%

The Challenging Pathway of Treatment for Neurogenesis Impairment in Down Syndrome: Achievements and Perspectives

Stagni

Bartesaghi

2022

Front. Cell. Neurosci.

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“…Moreover, the myelination process continues until after the postnatal stage ( 11 ). Hence, hPSC-derived glial cells have not been adequately applied to study many neurological diseases associated with the impaired functions of these glial types ( 12 ).…”

Section: Introductionmentioning

confidence: 99%

Direct Conversion to Achieve Glial Cell Fates: Oligodendrocytes and Schwann Cells

Yun

Kim

Lee

2022

IJSC

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Glia have been known for its pivotal roles in physiological and pathological conditions in the nervous system. To study glial biology, multiple approaches have been applied to utilize glial cells for research, including stem cell-based technologies. Human glial cells differentiated from pluripotent stem cells are now available, allowing us to study the structural and functional roles of glia in the nervous system, although the efficiency is still low. Direct conversion is an advanced strategy governing fate conversion of diverse cell types directly into the desired lineage. This novel strategy stands as a promising approach for preliminary research and regenerative medicine. Direct conversion employs genetic and environmental cues to change cell fate to that with the required functional cell properties while retaining maturity-related molecular features. As an alternative method, it is now possible to obtain a variety of mature cell populations that could not be obtained using conventional differentiation methods. This review summarizes current achievements in obtaining glia, particularly oligodendrocytes and Schwann cells.

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“…Complementing these approaches, the use of human induced pluripotent stem cells (hIPSCs) models, and the expanding numbers of neural and glial differentiation protocols 4 , provide systems to assess some of the early developmental aspects of SZ. An advantage of using hIPSC models is that the genetic background of the patient is present in the IPS and differentiated cells.…”

Section: Introductionmentioning

confidence: 99%

SOX10 Expression Levels may be a Critical Mediator of White Matter Deficits in Schizophrenia

Cohen

McPhie²,

Ren³

et al. 2022

Preprint

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Abnormalities of brain connectivity are consistently observed in individuals with schizophrenias (SZ). Underlying these anomalies, convergent in vivo, post-mortem, and genomic evidence suggest abnormal oligodendrocyte (OL) development and function, including lower in vivo myelination in SZ. Using patient derived induced pluripotent stem cells (IPSCs), we previously observed a significant and substantial reduction in the number of OLs produced in cells from the SZ group compared to the healthy control (HC) group. We also observed a correlation between white matter (WM) estimated in brain in vivo and the number of OLs produced in vitro. We have now characterized potential mediators that may contribute to the SZ-associated deficit in OL production. We ran quantitative real-time polymerase chain reaction (qRT-PCRs) to detect group-specific differences in key myelin pathway proteins. Significant reductions of PAX6 and SOX10 expression were seen in the SZ group. We focused on SOX10 since one of its functions is the commitment of precursor cells to an oligodendrocyte fate. Using an inducible lentiviral system, we expressed SOX10 in patterned neural stem cells (NSCs) and quantified the number of OLs produced. Expression of SOX10 rescued the SZ-associated deficit in OL production, indicating that reduced SOX10 may be a critical mediator of OL dysfunction in SZ. We then ran qRT-PCRs to screen mRNAs for three proteins (SOX9, QK1 and FEZ1) whose expression was directly influenced by SOX10 or directly influenced the expression of SOX10. We saw significant reductions of SOX9 expression and a reduction in QK1 expression in the SZ group. RNAseq analysis confirmed these gene expression changes.

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Growing Glia: Cultivating Human Stem Cell Models of Gliogenesis in Health and Disease

Cited by 20 publications

References 171 publications

The Challenging Pathway of Treatment for Neurogenesis Impairment in Down Syndrome: Achievements and Perspectives

The Challenging Pathway of Treatment for Neurogenesis Impairment in Down Syndrome: Achievements and Perspectives

Direct Conversion to Achieve Glial Cell Fates: Oligodendrocytes and Schwann Cells

SOX10 Expression Levels may be a Critical Mediator of White Matter Deficits in Schizophrenia

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