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Enhanced innate responses in microglia derived from retinoblastoma patient-specific iPSCs

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收录情况： ◇ SCIE

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机构： [1]Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

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关键词： cytokine innate immunity microglia RB1 retinoblastoma

摘要：

RB1 deficiency leads to retinoblastoma (Rb), the most prevalent intraocular malignancy. Tumor-associated macrophages (TAMs) are related to local inflammation disorder, particularly by increasing cytokines and immune escape. Microglia, the unique resident macrophages for retinal homeostasis, are the most important immune cells of Rb. However, whether RB1 deficiency affects microglial function remain unknown. In this study, microglia were successfully differentiated from Rb patient- derived human induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs), and then we investigated the function of RB1 in microglia by live imaging phagocytosis assay, immunofluorescence, RNA-seq, qRT-PCR, ELISA and retina organoids/microglia co-culturing. RB1 was abundantly expressed in microglia and predominantly located in the nucleus. We then examined the phagocytosis ability and secretion function of iMGs in vitro. We found that RB1 deficiency did not affect the expression of microglia-specific markers or the phagocytic abilities of these cells by live-imaging. Upon LPS stimulation, RB1-deficient microglia displayed enhanced innate immune responses, as evidenced by activated MAPK signaling pathway and elevated expression of IL-6 and TNF-α at both mRNA and protein levels, compared to wildtype microglia. Furthermore, retinal structure disruption was observed when retinal organoids were co-cultured with RB1-deficient microglia, highlighting the potential contribution of microglia to Rb development and potential therapeutic strategies for retinoblastoma.© 2024 Wiley Periodicals LLC.

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出版当年[2023]版：

大类 | 2 区医学

小类 | 2 区神经科学

最新[2025]版：

大类 | 2 区医学

小类 | 2 区神经科学

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Q1 NEUROSCIENCES

最新[2023]版：

Q1 NEUROSCIENCES

影响因子： 5.4 最新[2023版] 6.6 最新五年平均 6.2 出版当年[2022版] 7 出版当年五年平均 8.073 出版前一年[2021版] 5.4 出版后一年[2023版]

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第一作者机构： [1]Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

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通讯机构： [1]Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, China. [*1]Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730 China.

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