Astrocyte endfoot formation controls the termination of oligodendrocyte precursor cell perivascular migration during development

Su, Yixun; Wang, Xiaorui; Yang, Yu-Jian; Chen, Liang; Xia, Wenlong; Hoi, Kimberly K.; Li, Hui; Wang, Qi; Yu, Guangdan; Chen, Xiaoying; Wang, Shouyu; Wang, Yuxin; Xiao, Lan; Verkhratsky, Alexei; Fancy, Stephen P.J.; Yi, Chenju; Niu, Jianqin

doi:10.1016/j.neuron.2022.10.032

Cited by 23 publications

(11 citation statements)

References 64 publications

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“…It is important to emphasize that astrocytes interact with other glial cells, including microglia [179][180][181] and oligodendrocytes [182,183], and also with immune cells [184,185]. These interactions play a crucial role in both normal and disease conditions [185][186][187].…”

Section: Discussionmentioning

confidence: 99%

Shining the Light on Astrocytic Ensembles

Delgado

Navarrete

2023

Cells

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While neurons have traditionally been considered the primary players in information processing, the role of astrocytes in this mechanism has largely been overlooked due to experimental constraints. In this review, we propose that astrocytic ensembles are active working groups that contribute significantly to animal conduct and suggest that studying the maps of these ensembles in conjunction with neurons is crucial for a more comprehensive understanding of behavior. We also discuss available methods for studying astrocytes and argue that these ensembles, complementarily with neurons, code and integrate complex behaviors, potentially specializing in concrete functions.

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Section: Discussionmentioning

confidence: 99%

Shining the Light on Astrocytic Ensembles

Delgado

Navarrete

2023

Cells

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“…There are limited studies on whether and how ECs are directly beneficial to OPC differentiation; rather, it has been reported that rat primary ECs isolated from P14 inhibited OPC differentiation in co‐culture system (Su et al, 2023). However, we have demonstrated here that hiPSC‐ECs improved OPC differentiation after co‐culture for a longer period, supported by a higher number of MPB+ OLs with more complex morphology.…”

Section: Discussionmentioning

confidence: 99%

Human iPSC‐derived endothelial cells promote CNS remyelination via BDNF and mTORC1 pathway

Ma,

Zhang,

Yin

et al. 2023

Glia

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Damage of myelin is a component of many diseases in the central nervous system (CNS). The activation and maturation of the quiescent oligodendrocyte progenitor cells (OPCs) are the crucial cellular processes for CNS remyelination, which is influenced by neuroinflammation in the lesion microenvironment. Endothelial cells derived from human induced pluripotent stem cells (hiPSC‐ECs) have shown promise in restoring function in various preclinical animal models. Here we ask whether and whether transplantation of hiPSC‐ECs could benefit remyelination in a mouse model of CNS demyelination. Our results show that in vitro, hiPSC‐ECs increase OPC proliferation, migration and differentiation via secreted soluble factors including brain‐derived neurotrophic factor (BDNF). hiPSC‐ECs also promote the survival of oligodendrocyte lineage cells in vitro and in vivo. Transplantation of hiPSC‐ECs into a toxin‐induced demyelination lesion in mouse corpus callosum (CC) leads to increased density of oligodendrocyte lineage cells and level of myelin in demyelinated area, correlated with a decreased neuroinflammation and an increased proportion of pro‐regenerative M2 phenotype in microglia/macrophages. The hiPSC‐EC‐exposed oligodendrocyte lineage cells showed significant increase in the level of phosphorylated S6 ribosomal protein (pS6) both in vitro and in vivo, indicating an involvement of mTORC1 pathway. These results suggest that hiPSC‐ECs may benefit myelin protection and regeneration which providing a potential source of cell therapy for a wide range of diseases and injuries associated with myelin damage.

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“…Error bars represent SEM. No statistical methods were used to pre-determine sample sizes but our sample sizes are similar to those reported in previous publications 11,85 . Data distribution was assumed to be normal, but this was not formally tested.…”

Section: Quantification and Statistical Analysismentioning

confidence: 96%

Oligodendroglial precursors orchestrate immune network instigating early demyelination in experimental autoimmune encephalomyelitis

Wang,

Huang,

Zheng

et al. 2023

Preprint

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The immunomodulatory cellular network that triggers early inflammation and demyelination, the key steps in multiple sclerosis (MS) pathogenesis remains poorly characterized. Here, we demonstrate that overactivation of Wnt pathway promotes pathological transformation of oligodendrocyte precursor cells (OPCs) to replicate pathological OPCs in human MS. In mouse experimental autoimmune encephalomyelitis (EAE), pathological OPCs attract CD4+ T-helper 1 (Th1) cells into the spinal cord and brain through CC-chemokine ligand 4 (CCL4), whilst OPCs cooperate with Th1 cells inducing transformation of cytotoxic macrophages that execute early demyelination. Simultaneously, Th1 cells and cytotoxic macrophages upregulate Wnt signaling and CCL4 expression in OPCs, thus exerting positive feedback onto the OPC-immune cascade and establishing a vicious cycle propagating EAE pathogenesis. Breaking this cascade by targeting CCL4 reduces immune cell infiltration, alleviates demyelination, and attenuates EAE severity. Our findings demonstrate a closely coordinated network of OPCs and immune cells therefore providing an alternative insight into MS pathophysiology.

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Astrocyte endfoot formation controls the termination of oligodendrocyte precursor cell perivascular migration during development

Cited by 23 publications

References 64 publications

Shining the Light on Astrocytic Ensembles

Shining the Light on Astrocytic Ensembles

Human iPSC‐derived endothelial cells promote CNS remyelination via BDNF and mTORC1 pathway

Oligodendroglial precursors orchestrate immune network instigating early demyelination in experimental autoimmune encephalomyelitis

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