The gene expression of primitive macrophage derived from human induced pluripotent stem cells treated by PNU282987
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE295886 | GEO | 2026/06/01
REPOSITORIES: GEO
Similar Datasets
Project description:Microglia arise exclusively from yolk sac (YS) progenitors during primitive hematopoiesis, while other tissue resident macrophages (TRMs)originate during transient-definitive and definitive hematopoiesis. Macrophages require the transcriptional repressor Zeb2 for development, and macrophages developing during definitive hematopoiesis require the ‒165 kb Zeb2 enhancer. However, microglia develop normally in Zeb2 ‒165kb mice lacking this enhancer, indicating that a distinct genetic program supports macrophage development in primitive hematopoiesis. Here, we identify the molecular basis that distinguishes macrophage development in primitive vs. definitive hematopoiesis. We show that all tissue resident macrophages (TRMs) that develop in Zeb2 ‒165kb mice arise exclusively during primitive hematopoiesis, showing that even erythro-myeloid progenitors (EMPs) from the transient-definitive stage rely on the ‒165 Zeb2 enhancer. Next, we identified the transcription factors Maf and Jun as being expressed by yolk sac (YS) progenitors during primitive hematopoiesis, but not by progenitors during definitive hematopoiesis. Further, we find that Maf and Jun together induce Zeb2 expression independently of the ‒165 kb Zeb2 enhancer and restore macrophage development from adult bone marrow progenitors in Zeb2 ‒165kb mice. Finally, Maf-deficient embryos show severe ablation of microglia development, confirming the in vivo requirement for Maf in supporting Zeb2 during primitive hematopoiesis. These results illustrate distinct transcriptional pathways controlling macrophage development during primitive and subsequent waves of hematopoiesis.
2025-12-26 | GSE304528 | GEO
Project description:We sequenced mRNA from 7 microglia extracted from sheep fetuses exposed to LPS, agonist and antagonist of α7 nicotinic acetylcholine receptor to determine signaling pathway through modeling of α7 during inflammation.
2017-08-11 | GSE101857 | GEO
Project description:Neuroinflammation influences the development of chronic pain, an increasingly prevalent condition impacting the lives of many worldwide. Given the challenges of managing chronic pain, it is essential to explore new neuroimmune targets for the development of safe and effective analgesics. Alpha 7 nicotinic acetylcholine receptors (α7 nAChRs) have been explored for their role in pain and inflammation. We hypothesize that α7 nAChR expression within myeloid cells mediates an anti-inflammatory response that mitigates pain states. We engineered mice with deletion of the α7 gene (Chrna7) from myeloid lineage cells conditionally using LysM-Cre. We characterized these mice in chemotherapy-induced peripheral neuropathy (CIPN) using paclitaxel. RNA-sequencing and pathway enrichment analysis of spinal cord tissues from mice treated with paclitaxel were performed. Our study suggests α7 nAChR expression in myeloid cells mediates an endogenous cholinergic anti-inflammatory pathway, which plays a critical role in chronic neuropathic and inflammatory pain.
2026-02-11 | GSE318938 | GEO
Project description:Humans recover from hepatic injury largely by liver regeneration. This complicated process requires hepatocyte proliferation driven by collaboration amongst multiple hepatic cell types. Immune cells also contribute, with some producing mitogenic cytokines such as IL-6 but others damaging hepatocytes by secreting IFNγ. A better understanding of immune cell functions in liver regeneration is necessary to improve clinical interventions. Here, we demonstrate that B cells expressing choline acetyltransferase (ChAT), the enzyme synthesizing acetylcholine (ACh), are specifically required for liver regeneration. Mice lacking ChAT+ B cells subjected to partial hepatectomy (PHX) display greater mortality due to failed liver regeneration. We show that both Kupffer cells and hepatic CD8+ T cells express the α7 nicotinic ACh receptor (nAChR; encoded by Chrna7), and that liver regeneration is also disrupted in mice lacking α7 nAChR. Thus, two regulatory axes promoting hepatocyte proliferation operate following PHX: one where hepatic ChAT+ B cells and α7 nAChR+ Kupffer cells interact to drive IL-6 production by Kupffer cells, and another where ChAT+ B cells and α7 nAChR+ hepatic CD8+ T cells interact to reduce IFNγ production by CD8+ T cells. Our work offers novel insights into liver regeneration mechanisms that may point to new therapies for liver damage.
2025-05-02 | GSE283288 | GEO
Project description:Humans recover from hepatic injury largely by liver regeneration. This complicated process requires hepatocyte proliferation driven by collaboration amongst multiple hepatic cell types. Immune cells also contribute, with some producing mitogenic cytokines such as IL-6 but others damaging hepatocytes by secreting IFNγ. A better understanding of immune cell functions in liver regeneration is necessary to improve clinical interventions. Here, we demonstrate that B cells expressing choline acetyltransferase (ChAT), the enzyme synthesizing acetylcholine (ACh), are specifically required for liver regeneration. Mice lacking ChAT+ B cells subjected to partial hepatectomy (PHX) display greater mortality due to failed liver regeneration. We show that both Kupffer cells and hepatic CD8+ T cells express the α7 nicotinic ACh receptor (nAChR; encoded by Chrna7), and that liver regeneration is also disrupted in mice lacking α7 nAChR. Thus, two regulatory axes promoting hepatocyte proliferation operate following PHX: one where hepatic ChAT+ B cells and α7 nAChR+ Kupffer cells interact to drive IL-6 production by Kupffer cells, and another where ChAT+ B cells and α7 nAChR+ hepatic CD8+ T cells interact to reduce IFNγ production by CD8+ T cells. Our work offers novel insights into liver regeneration mechanisms that may point to new therapies for liver damage.
2025-05-02 | GSE283252 | GEO
Project description:The regulation of developmental haematopoiesis by the bHLH transcription factor Lyl-1 has been the focus of our present study. Analysing how Lyl-1 may impact mouse developmental haematopoiesis indicated that Lyl-1 marks YS-derived primitive macrophage progenitors, as well as embryonic microglia. During ontogeny, microglia which representtissue macrophages of the central nervous system emerge from haematopoietic stem cell-independent progenitors originating from the yolk sac (YS). Activation of microglia during development is often critical and my lead to neuropsychiatric diseases in the adult. Here, we show that Lyl-1 disruption alters the development of microglia with far reaching consequences. Lyl-1-deficiency leads to decreased dendritic spine density and impaired neuronal activity, as well as impaired social interactions with increased anxiety-like behaviour. We thus identify Lyl-1 as a critical regulator of primitive macrophage and microglia development, whose disruption impacts microglia development and functionality, leading to a distinct neuropsychiatric phenotype.
2025-03-11 | GSE128378 | GEO
Project description:The earliest macrophages are generated during embryonic development from erythro-myeloid progenitors (EMPs) via primitive haematopoiesis. This process is poorly understood in humans and in the mouse is thought to be spatially restricted to the yolk sac. Human fetal placental macrophages, Hofbauer cells (HBC), arise during the primitive haematopoietic wave at ~18 days post conception. Here we identify a population of placental erythro-myeloid progenitors (PEMPs) in the early human placenta that give rise to HBC. PEMP are fetal CD34+CD43+ progenitors found exclusively at early gestational timepoints. Transcriptomic analyses reveal that PEMP have conserved features of primitive yolk sac EMPs, including the lack of HLF expression. Using in vitro single-cell culture experiments we show that PEMP generate HBC-like cells that completely lack HLA-DR expression and demonstrate that this is a conserved feature of all macrophages generated by primitive haematopoiesis in humans. Finally, we demonstrate that the class II transactivator, CTIIA, the master regulator HLA-DR expression, is epigenetically silenced during primitive haematopoiesis, leading to HLA-DRneg macrophages. These findings demonstrate that HBC are derived locally from PEMP and establish the human placenta as an additional site of primitive haematopoiesis.
2023-08-01 | GSE210868 | GEO
Project description:The earliest macrophages are generated during embryonic development from erythro-myeloid progenitors (EMPs) via primitive haematopoiesis. This process is poorly understood in humans and in the mouse is thought to be spatially restricted to the yolk sac. Human fetal placental macrophages, Hofbauer cells (HBC), arise during the primitive haematopoietic wave at ~18 days post conception. Here we identify a population of placental erythro-myeloid progenitors (PEMPs) in the early human placenta that give rise to HBC. PEMP are fetal CD34+CD43+ progenitors found exclusively at early gestational timepoints. Transcriptomic analyses reveal that PEMP have conserved features of primitive yolk sac EMPs, including the lack of HLF expression. Using in vitro single-cell culture experiments we show that PEMP generate HBC-like cells that completely lack HLA-DR expression and demonstrate that this is a conserved feature of all macrophages generated by primitive haematopoiesis in humans. Finally, we demonstrate that the class II transactivator, CTIIA, the master regulator HLA-DR expression, is epigenetically silenced during primitive haematopoiesis, leading to HLA-DRneg macrophages. These findings demonstrate that HBC are derived locally from PEMP and establish the human placenta as an additional site of primitive haematopoiesis.
| EGAS00001006981 | EGA
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.
2017-07-20 | GSE99078 | GEO
Project description:Primitive macrophages enhance a perivascular niche to enable vascular perfusion in human cardiac tissue The intricate anatomical structure and high cellular density of the myocardium significantly complicate the bioengineering of vascular networks within cardiac tissues, creating challenges in establishing a perfusable and stable vasculature within these tissues. Emerging evidence from murine in vivo studies underscores the significant role of resident cardiac macrophages in facilitating cardiac regeneration post-injury, specifically their role in enhancing angiogenesis. Here, for the first time, we integrate human pluripotent stem cell derived macrophages, resembling primitive yolk-sac derived macrophages, within human in vitro vascularized heart-on-chip platforms. The incorporation of primitive macrophages had a profound impact on the long term functionality of microvascularized cardiac tissue, particularly in enabling formation of perfusable vasculature with a stable barrier function that persisted for two weeks in culture. These effects were contingent on physical cell-cell interactions and significantly diminished in transwell culture. The inclusion of primitive macrophages mitigated tissue cytotoxicity and curtailed the release of cell-free mitochondrial-DNA, underscoring their indispensable role for mitigating cell damage in bioengineered tissues. Furthermore, their incorporation upregulated the secretion of pro-angiogenic, matrix remodeling and cardioprotective cytokines such as MMP-12, MMP-2, Angiopoietin-like 1, NRG-3, SIGIRR and Adiponectin. RNA sequencing disclosed upregulation of cardiac maturation (TTNI3, SCN5A, MYL2, and RYR2), and endothelial cells genes (PDGF-B, PECAM-1 and CDH5) as well as enhancement of angiogenic signaling, Wnt and PDGF pathways. Collectively, our results offer valuable insights into the integral role of primitive macrophages in directing long-term functional vascularization of cardiac tissues, paving the way for novel therapeutic strategies and advancing heart-on-a-chip systems.
2025-08-04 | PXD044560 | Pride