Identity and Maturity of iPSC-Derived Oligodendrocytes in 2D and Organoid Systems

Cells, Год журнала: 2024, Номер 13(8), С. 674 - 674

Опубликована: Апрель 13, 2024

Oligodendrocytes originating in the brain and spinal cord as well ventral dorsal domains of neural tube are transcriptomically functionally distinct. These distinctions also reflected ultrastructure produced myelin, susceptibility to myelin-related disorders, which highlights significance choice patterning protocols differentiation induced pluripotent stem cells (iPSCs) into oligodendrocytes. Thus, our first goal was survey different approaches applied generation iPSC-derived oligodendrocytes 2D culture organoids, reflect on how these pertain regional spatial fate generated oligodendrocyte progenitors myelinating This knowledge is increasingly important disease modeling future therapeutic strategies. Our second recap recent advances development oligodendrocyte-enriched we explore their relevance a specification alongside duration, complexity, maturation stages myelin biology. Finally, discuss shortcomings existing potential explorations.

Язык: Английский

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In vitro models for human neuroglia

Handbook of clinical neurology, Год журнала: 2025, Номер unknown, С. 213 - 227

Опубликована: Янв. 1, 2025

Язык: Английский

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Intracellular calcium dysregulation in heart and brain diseases: Insights from induced pluripotent stem cell studies

Journal of Neuropathology & Experimental Neurology, Год журнала: 2024, Номер 83(12), С. 993 - 1002

Опубликована: Июль 13, 2024

Abstract The central nervous system (CNS) plays a role in regulating heart rate and myocardial contractility through sympathetic parasympathetic nerves, the can impact functional equilibrium of CNS feedback signals. Although brain diseases often coexist mutually influence each other, potential links between remain unclear due to lack reliable models these relationships. Induced pluripotent stem cells (iPSCs), which differentiate into multiple cell types, biology regenerative medicine may offer tools clarify mechanisms relationships facilitate screening effective therapeutic agents. Because calcium ions play essential roles both cardiovascular systems, this review addresses how recent iPSC disease reveal dysregulation intracellular might be common pathological factor underlying diseases.

Язык: Английский

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Human iPSC-derived myelinating organoids and globoid cells to study Krabbe Disease

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июль 23, 2024

Abstract Krabbe disease (Kd) is a lysosomal storage disorder (LSD) caused by the deficiency of galactosylceramidase (GALC) which cleaves myelin enriched lipid galactosylceramide (GalCer). Accumulated GalCer catabolized into cytotoxic psychosine that causes myelinating cells death and demyelination recruits microglia/macrophages fail to digest debris become globoid cells. Here, understand pathological mechanisms Kd, we used induced pluripotent stem (iPSCs) from Kd patients produce organoids microglia. We show have no obvious defects in neurogenesis, astrogenesis, oligodendrogenesis but manifest early myelination defects. Specifically, showed shorter similar number internodes than Controls at peak reduced later time point. Interestingly, affected absence autophagy mTOR pathway dysregulation, suggesting lack dysfunction makes this organoid model very valuable tool study events drive Kd. iPSC-derived microglia marginal rate cell formation under normal culture conditions drastically increased upon feeding. Under conditions, minor LAMP1 content decrease slight increase protein LC3B. Upon feeding, accumulation proteins strong reduction point are reverted showing compensatory capabilities Altogether, supports value our cultures as tools mechanism play overcome

Язык: Английский

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Human iPSC-derived myelinating organoids and globoid cells to study Krabbe disease

PLoS ONE, Год журнала: 2024, Номер 19(12), С. e0314858 - e0314858

Опубликована: Дек. 5, 2024

Krabbe disease (Kd) is a lysosomal storage disorder (LSD) caused by the deficiency of galactosylceramidase (GALC) which cleaves myelin enriched lipid galactosylceramide (GalCer). Accumulated GalCer catabolized into cytotoxic psychosine that causes myelinating cells death and demyelination recruits microglia/macrophages fail to digest debris become globoid cells. Here, understand pathological mechanisms Kd, we used induced pluripotent stem (iPSCs) from Kd patients produce organoids microglia. We show have no obvious defects in neurogenesis, astrogenesis, oligodendrogenesis but manifest early myelination defects. Specifically, showed shorter similar number internodes than Controls at peak reduced later time point. Interestingly, affected absence autophagy mTOR pathway dysregulation, suggesting lack dysfunction makes this organoid model very valuable tool study events drive Kd. iPSC-derived microglia marginal rate cell formation under normal culture conditions drastically increased upon feeding. Under conditions, minor LAMP1 content decrease slight increase protein LC3B. Upon feeding, accumulation proteins strong reduction point are reverted showing compensatory capabilities Altogether, supports value our cultures as tools mechanism play overcome

Язык: Английский

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The long road to the development of stem cells as a model for central nervous system health and disease

Advances in neurotoxicology, Год журнала: 2024, Номер unknown, С. 1 - 45

Опубликована: Янв. 1, 2024

Язык: Английский

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Harnessing stem cell-based approaches for clinically meaningful discoveries in schizophrenia

Schizophrenia Research, Год журнала: 2024, Номер 273, С. 1 - 3

Опубликована: Авг. 29, 2024

Язык: Английский

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