Differentiation of human and murine induced pluripotent stem cells to microglia-like cells
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PROVIDER: PRJNA312650 | ENA |
REPOSITORIES: ENA
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Project description:Microglia are the resident inflammatory cells of the central nervous system (CNS) and have important roles in development, homeostasis and a variety of neurologic and psychiatric diseases. Difficulties in procuring human microglia have limited their study and hampered the clinical translation of microglia-based treatments shown to be effective in animal disease models. Here, we report the differentiation of human induced pluripotent stem cells (iPSC) into microglia-like cells by exposure to defined factors and co-culture with astrocytes. These iPSC-derived microglia (iPS-MG) have the phenotype, gene expression profile and functional properties of brain-isolated microglia. Murine iPS-MG generated using a similar protocol have equivalent efficacy to primary brain-isolated microglia in the treatment of murine syngeneic intracranial malignant gliomas. The ability to generate human microglia facilitates the further study of this important CNS cell type and raises the possibility of their use in personalized medicine applications.
2017-03-02 | GSE47605 | GEO
Project description:Microglia are myeloid-lineage inflammatory cells that activate innate and adaptive immune responses within the central nervous system (CNS). They also have important roles in CNS development and homeostasis and can modulate the course of a variety of CNS diseases. We report here the sequential differentiation of murine induced pluripotent stem cells (iPSC) into hematopoietic progenitor-like cells and then into cells with a phenotype and gene expression profile resembling that of primary brain-isolated microglia. Functionally, the iPSC-derived microglia (iPS-MG) produce inflammatory cytokines and reactive oxygen species, demonstrate phagocytic activity and migrate to areas of pathology within the brain following intracranial injection. The ability to readily generate iPS-MG in vitro will facilitate the study of normal and disease-specific microglia and be useful for the development of microglia-based treatments for CNS diseases.
2017-03-02 | GSE78115 | GEO
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Project description:Microglia, the immune cells of the brain, are crucial to proper development and maintenance of the central nervous system, and their involvement in numerous neurological disorders is increasingly being recognized. To improve our understanding of human microglial biology, we devised a chemically defined protocol to generate human microglia from pluripotent stem cells. Myeloid progenitors expressing CD14/CX3CR1 were generated within 30 days of differentiation from both embryonic and induced pluripotent stem cells (iPSCs). Further differentiation of the progenitors resulted in ramified microglia with highly motile processes, expressing typical microglial markers. Analyses of gene expression and cytokine release showed close similarities between iPSC-derived (iPSC-MG) and human primary microglia as well as clear distinctions from macrophages. iPSC-MG were able to phagocytose and responded to ADP by producing intracellular Ca2+ transients, whereas macrophages lacked such response. The differentiation protocol was highly reproducible across several pluripotent stem cell (PSC) lines.
2017-04-13 | GSE97744 | GEO
Project description:Microglia-like cells and neural cells were generated from several hES and hIPS lines. As subset was characterized by RNA seq and compared to expression profiles of published primary and induced samples. ABSTRACT: Microglia, the only lifelong resident immune cells of the central nervous system (CNS), are highly specialized macrophages which have been recognized to play a crucial role in neurodegenerative diseases such as Alzheimer’s, Parkinson’s and Adrenoleukodystrophy (ALD). However, in contrast to other cell types of the human CNS, bona fide microglia have not yet been derived from cultured human pluripotent stem cells. Here we establish a robust and efficient protocol for the rapid production of microglia-like cells from human embryonic stem (ES) and induced pluripotent stem (iPS) cells that uses defined serum-free culture conditions. These in vitro pluripotent stem cell-derived microglia-like cells (termed pMGLs) faithfully recapitulate the expected ontogeny and characteristics of their in vivo counterparts and resemble primary fetal human and mouse microglia. We generated these cells from multiple disease-specific cell lines, and find that pMGLs derived from MeCP2 mutant hES cells are smaller than their isogenic controls. We further describe a culture platform to study integration and live behavior of pMGLs in organotypic 3D-cultures. This modular differentiation system allows the study of microglia in highly defined conditions, as they mature in response to developmentally relevant cues, and provides a framework to study the long-term interaction of microglia residing in a tissue-like environment.
2016-09-26 | GSE85839 | GEO
Project description:mouse embryonic fibroblasts, embryonic stem cells, and induced pluripotent stem cells were compared via metabolomic analysis
2018-08-02 | MSV000082680 | GNPS
Project description:Microglia, the immune cells of the central nervous system (CNS), play critical roles in brain physiology and pathology. We report a novel approach that produces within ten days the differentiation of human induced pluripotent stem cells (hiPSCs) into microglia (iMG) by forced expression of both SPI1 and CEBPA. High-level expression of the main microglial markers and the purity of the iMG cells were confirmed by RT-qPCR, immunostaining and flow cytometry analyses. Whole transcriptome analysis demonstrated that these iMGs resemble human fetal/adult microglia but not human monocytes. Moreover, these iMGs exhibited appropriate physiological functions, including various inflammatory responses, ADP/ATP-evoked migration and phagocytic ability. When co-cultured with hiPSC-derived neurons (iNs), the iMGs respond and migrate toward injured neurons. This study has established a protocol for the rapid conversion of hiPSCs into functional iMGs, which should facilitate functional studies of human microglia using different disease models and also help with drug discovery.
2021-04-08 | GSE163984 | GEO
Project description:Neurofibromatosis type 1 (NF1) is autosomal dominant condition caused by germline mutations in the NF1 gene on chromosome 17. Children with NF1 are prone to the development of multiple nervous system abnormalities, including autism and brain tumors, which could result from the effect of NF1 mutation on microglia function. Using Nf1-mutant mice, we previously identified impaired microglia process extension and phagocytosis resulting from defects in purinergic signaling. To determine whether these abnormalities are also observed in human microglia, we leveraged human induced pluripotent stem cell engineering to generate human microglia-like (hiMGL) cells harboring three different NF1 patient-derived NF1 gene mutations. Both NF1-mutant and isogenic control hiMGL cells express classical microglial markers and exhibit similar transcriptomes and cytokine/chemokine release profiles, NF1-mutant hiMGL cells have defects in P2X receptor activation, phagocytosis and motility. We conclude that NF1 mutation impairs some aspects of microglia function in humans, which could contribute to a subset of the neurological abnormalities seen in children with NF1.
2023-12-14 | GSE203647 | GEO
Project description:Specialized tissue macrophages arise during embryogenesis from yolk-sac (YS) progenitors that migrate into developing tissues and terminally differentiate in situ. Until recently, it has been impossible to isolate or derive sufficient numbers of YS-derived macrophages for further study, but data now suggest that induced pluripotent stem cells (iPSCs) can be driven to undergo a process reminiscent of YS-hematopoiesis in vitro. We asked whether iPSC-derived primitive macrophages (iMac) can terminally differentiate into specialized macrophages using growth factors and organ-specific cues. Co-culturing murine iMac with iPSC-derived neurons promoted differentiation into microglia-like cells in vitro. Furthermore, murine iMac differentiated in vivo into microglia following injection into the brain, and functional alveolar macrophages after engraftment in the lung.
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