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Project description:HIV-associated neurocognitive disorders (HAND) persist as a notable cause of illness among individuals with HIV. Despite significant progress in antiretroviral therapy (ART), HAND continues to be a major concern, impacting approximately one-third of those infected with HIV. Recent research underscores the pivotal role of microglia, the primary immune cells in the central nervous system (CNS), in the development and progression of HAND. The infection and activation of microglia by HIV leads to the release of pro-inflammatory markers, cytokines, chemokines, secondary messengers, and reactive oxygen species (ROS). These factors collectively initiate signalling pathways that contribute to neuroinflammation, a central process in the development of HAND. In order to validate stem cell-derived microglia (iMGL) as a viable model system for HAND investigation, we infected iMGLs and human monocyte-derived macrophages (MDMs) with the primary HIV-1 isolate Ba-L at an MOI of 0.25. Total RNA was extracted from cell populations on days 1, 2, 4, 6, and 8 following infection. Subsequently, we conducted bulk RNA sequencing to examine the longitudinal transcriptomic alterations induced by the virus over this time frame
2024-05-01 | GSE248998 | GEO
Project description:HIV-associated neurocognitive disorders (HAND) persist as a notable cause of illness among individuals with HIV. Despite significant progress in antiretroviral therapy (ART), HAND continues to be a major concern, impacting approximately one-third of those infected with HIV. Recent research underscores the pivotal role of microglia, the primary immune cells in the central nervous system (CNS), in the development and progression of HAND. The infection and activation of microglia by HIV leads to the release of pro-inflammatory markers, cytokines, chemokines, secondary messengers, and reactive oxygen species (ROS). These factors collectively initiate signalling pathways that contribute to neuroinflammation, a central process in the development of HAND. In order to validate stem cell-derived microglia (iMGL) as a viable model system for HAND investigation, we infected iMGLs and human monocyte-derived macrophages (MDMs) with the primary HIV-1 isolate Ba-L at an MOI of 0.25. Total RNA was extracted from cell populations on days 1, 2, 4, 6, and 8 following infection. Subsequently, we conducted bulk RNA sequencing to examine the longitudinal transcriptomic alterations induced by the virus over this time frame
2024-05-01 | GSE248997 | GEO
Project description:HIV-associated neurocognitive disorders (HAND) persist as a notable cause of illness among individuals with HIV. Despite significant progress in antiretroviral therapy (ART), HAND continues to be a major concern, impacting approximately one-third of those infected with HIV. Recent research underscores the pivotal role of microglia, the primary immune cells in the central nervous system (CNS), in the development and progression of HAND. The infection and activation of microglia by HIV leads to the release of pro-inflammatory markers, cytokines, chemokines, secondary messengers, and reactive oxygen species (ROS). These factors collectively initiate signalling pathways that contribute to neuroinflammation, a central process in the development of HAND. In order to validate stem cell-derived microglia (iMGL) as a viable model system for HAND investigation, we infected iMGLs and human monocyte-derived macrophages (MDMs) with the primary HIV-1 isolate Ba-L at an MOI of 0.25. Total RNA was extracted from cell populations on days 1, 2, 4, 6, and 8 following infection. Subsequently, we conducted bulk RNA sequencing to examine the longitudinal transcriptomic alterations induced by the virus over this time frame
2024-05-01 | GSE248996 | GEO
Project description:Stem Cell-derived Microglia Exhibit HAND Gene Expression Signature Early Upon Infection with HIV-1
| PRJNA1046554 | ENA
Project description:Stem Cell-derived Microglia Exhibit HAND Gene Expression Signature Early Upon Infection with HIV-1 [iPSCMG_TFS]
| PRJNA1046560 | ENA
Project description:Stem Cell-derived Microglia Exhibit HAND Gene Expression Signature Early Upon Infection with HIV-1 [MDM]
| PRJNA1046559 | ENA
Project description:Stem Cell-derived Microglia Exhibit HAND Gene Expression Signature Early Upon Infection with HIV-1 [iPSCMG]
| PRJNA1046558 | ENA
Project description:Optimal cell-based therapies for the treatment of muscle degenerative disorders should not only regenerate fibers but provide a quiescent satellite cell pool ensuring long-term maintenance and regeneration. Conditional expression of Pax3/Pax7 in differentiating pluripotent stem cells (PSCs) allows the generation of myogenic progenitors endowed with enhanced regenerative capacity. To identify the molecular determinants underlying their regenerative potential, we performed transcriptome analyses of these cells along with primary myogenic cells from several developmental stages. Here we show that in vitro-generated PSC-derived myogenic progenitors possess a molecular signature similar to embryonic/fetal myoblasts. However, compared with fetal myoblasts, following transplantation they show superior myofiber engraftment and ability to seed the satellite cell niche, respond to multiple reinjuries, and contribute to long-term regeneration. Upon engraftment, the transcriptome of reisolated Pax3/Pax7-induced PSC-derived myogenic progenitors changes toward a postnatal molecular signature, particularly in genes involved in extracellular matrix remodeling. These findings demonstrate that Pax3/Pax7-induced myogenic progenitors remodel their molecular signature and functionally mature upon in vivo exposure to the adult muscle environment.
| S-EPMC6410870 | biostudies-literature
Project description:BackgroundWidescale evidence points to the involvement of glia and immune pathways in the progression of Alzheimer's disease (AD). AD-associated iPSC-derived glial cells show a diverse range of AD-related phenotypic states encompassing cytokine/chemokine release, phagocytosis and morphological profiles, but to date studies are limited to cells derived from PSEN1, APOE and APP mutations or sporadic patients. The aim of the current study was to successfully differentiate iPSC-derived microglia and astrocytes from patients harbouring an AD-causative PSEN2 (N141I) mutation and characterise the inflammatory and morphological profile of these cells.MethodsiPSCs from three healthy control individuals and three familial AD patients harbouring a heterozygous PSEN2 (N141I) mutation were used to derive astrocytes and microglia-like cells and cell identity and morphology were characterised through immunofluorescent microscopy. Cellular characterisation involved the stimulation of these cells by LPS and Aβ42 and analysis of cytokine/chemokine release was conducted through ELISAs and multi-cytokine arrays. The phagocytic capacity of these cells was then indexed by the uptake of fluorescently-labelled fibrillar Aβ42.ResultsAD-derived astrocytes and microglia-like cells exhibited an atrophied and less complex morphological appearance than healthy controls. AD-derived astrocytes showed increased basal expression of GFAP, S100β and increased secretion and phagocytosis of Aβ42 while AD-derived microglia-like cells showed decreased IL-8 secretion compared to healthy controls. Upon immunological challenge AD-derived astrocytes and microglia-like cells showed exaggerated secretion of the pro-inflammatory IL-6, CXCL1, ICAM-1 and IL-8 from astrocytes and IL-18 and MIF from microglia.ConclusionOur study showed, for the first time, the differentiation and characterisation of iPSC-derived astrocytes and microglia-like cells harbouring a PSEN2 (N141I) mutation. PSEN2 (N141I)-mutant astrocytes and microglia-like cells presented with a 'primed' phenotype characterised by reduced morphological complexity, exaggerated pro-inflammatory cytokine secretion and altered Aβ42 production and phagocytosis.
| S-EPMC10765839 | biostudies-literature
Project description:Disseminated toxoplasmosis in the central nervous system (CNS) is often accompanied by a lethal outcome. Studies with murine models of infection have focused on the role of systemic immunity in control of toxoplasmic encephalitis, while knowledge remains limited on the contributions of resident cells with immune functions in the CNS. In this study, the role of glial cells was addressed in the setting of recrudescent Toxoplasma infection in mice. Activated astrocytes and microglia were observed in the close vicinity of foci with replicating parasites in situ in the brain parenchyma. Toxoplasma gondii tachyzoites were allowed to infect primary microglia and astrocytes in vitro. Microglia were permissive to parasite replication, and infected microglia readily transmigrated across transwell membranes and cell monolayers. Thus, infected microglia, but not astrocytes, exhibited a hypermotility phenotype reminiscent of that recently described for infected dendritic cells. In contrast to gamma interferon-activated microglia, Toxoplasma-infected microglia did not upregulate major histocompatibility complex (MHC) class II molecules and the costimulatory molecule CD86. Yet Toxoplasma-infected microglia and astrocytes exhibited increased sensitivity to T cell-mediated killing, leading to rapid parasite transfer to effector T cells in vitro. We hypothesize that glial cells and T cells, besides their role in triggering antiparasite immunity, may also act as "Trojan horses," paradoxically facilitating dissemination of Toxoplasma within the CNS. To our knowledge, this constitutes the first report of migratory activation of a resident CNS cell by an intracellular parasite.
| S-EPMC3147544 | biostudies-literature