Gene expression profile at single cell level of mononuclear cells from the liver sinusoid
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE200173 | GEO | 2022/08/08
REPOSITORIES: GEO
Similar Datasets
Project description:CD8+ T cells, critical mediators of adaptive immunity, may also exhibit innate-like properties, such as surface expression of NKG2C, an activating receptor typically associated with natural killer (NK) cells. We demonstrate that, similar to NK cells, NKG2C+TCRαβ+CD8+ T cells are associated with prior HCMV exposure. In addition to expressing several NK cell markers (CD56, KIR), NKG2C+CD8+ T cells are oligoclonal and do not upregulate PD1 despite chronic activation. Furthermore, NKG2C+CD8+ T cells from some individuals exhibit high effector function against leukemia cells and HCMV-infected fibroblasts, dictated by NKG2C and TCR specificity. Importantly, we observe that co-triggering of CD3 and NKG2C results in increased degranulation and IFN-γ production by NKG2C+CD8+ T cells in an additive fashion. Transcriptomic analysis reveals that the transcription factor BCL11B, a regulator of T cell developmental fate, is significantly down-modulated in NKG2C+CD8+ T cells when compared to conventional NKG2C-CD8+ T cells. BCL11B deletion in conventional CD8 T cells results in the emergence of a CD56+CD94+DAP12+NKG2C+CD45RA+CCR7-PD1-/low T cell population with activity against HLA-E+ targets. Given their intrinsic capacity to recognize diseased cells coupled with lack of PD-1 upregulation despite chronic stimulation, NKG2C+CD8+ T cells represent a novel lymphocyte population that straddles the boundary between innate and adaptive immunity, presenting an attractive alternative for cellular therapy, including CAR T-based therapies.
2021-10-14 | GSE179981 | GEO
Project description:The liver is an immunologically unique organ in terms of the regulation of immuno-tolerance and immune responses. Recently, non-recirculating tissue-resident memory T (TRM) cells expressing CD69 were found in various peripheral organs. In humans, a large population of CD69+CD8+ memory T cells residing in liver sinusoids shows reduced cytotoxicity. However, the trascriptional characteristics of human liver CD8+ T cells are still unknown. Therefore, we performed a microarray analysis to screen the gene expression profile in liver sinusoidal CD8+ T cells using CMV-specific CD8+ T cells from human peripheral blood and liver sinusoid.
2019-12-06 | GSE141508 | GEO
Project description:Previous research on adaptive NK cells in rhesus macaques suffered from the lack of specific antibodies to differentiate between inhibitory CD94/NKG2A and stimulatory CD94/NKG2C heterodimeric receptors. Recently we reported an expansion of NKG2C receptor-encoding genes in rhesus macaques, but their expression and functional role on primary NK cells remained unknown due to this deficit. Thus, we established monoclonal antibodies 4A8 and 7B1 which show identical specificities and bind to both NKG2C-1 and NKG2C-2 but neither react with NKG2C-3 nor NKG2A on transfected cell lines. Using a combination of 4A8 and Z199 antibodies in multicolor flow cytometry we detected broad expression (4-73%) of NKG2C-1 and/or NKG2C-2 (NKG2C-1/2) on primary NK cells in rhesus macaques from our breeding colony. Stratifying our data to CMV-positive and CMV-negative animals, we noticed a higher proportion (23-73%) in primary NK cells expressing NKG2C-1/2 in CMV+ as compared to CMV- macaques (4-5%). These NKG2C-1/2-positive NK cells in CMV+ macaques are characterized by lower expression of IL12RB2, ZBTB16 and SH2D1B as well as high expression of IFN-gamma, indicating that antibody 4A8 detects CMV-associated adaptive NK cells. Single cell RNA seq data of 4A8-positive NK cells from a CMV-positive individual demonstrated that a high proportion of these adaptive NK cells transcribe in addition to NKG2C-1/2 also NKG2C-3, but interestingly NKG2A as well. Remarkably, NKG2C-1 and in particular NKG2C-2 have a higher affinity to Mamu-E as compared to NKG2A. Primary NK cells exposed to Mamu-E-expressing target cells displayed strong degranulation as well as IFN-gamma expression of 4A8+ adaptive NK cells of rhCMV+ animals that was not evident in rhCMV- animals. Thus, despite co-expression of inhibitory and stimulatory CD94/NKG2 receptors the higher number of different stimulatory NKG2C receptors and their higher binding avidity to Mamu-E outreach inhibitory signaling via NKG2A. These data demonstrate the evolutionary conservation of the CMV-driven development of NKG2C-positive adaptive NK cells with particular molecular signatures in primates and with changes in gene copy numbers and regulation and in ligand binding strength of NKG2C isotypes. Thus, rhesus macaques represent a suitable and valuable nonhuman primate animal model to study the CMV-NKG2C liaison in vivo.
2022-09-07 | GSE211613 | GEO
Project description:We report the gene expression profiles of liver sinusoidal Vγ9+Vδ2+ T cells from healthy donors and patients with hepatitis B virus-related chronic liver disease.
2021-01-06 | GSE164266 | GEO
Project description:There is limited knowledge on the origin and development of the ample spectrum of human NK cells, particularly of specialized NK subsets. Here, we characterized the NK cell progeny of CD34+DNAM-1bright CXCR4+ precursors that reside in healthy bone marrow and circulate in the peripheral blood (PB) of patients with chronic infections/inflammation. including HIV, HCV or HCMV reactivation after HSC transplantation. Unlike conventional CD34+ precursors they rapidly differentiated in vitro into cytotoxic, IFNγ-secreting CD94/NKG2C+KIR+CD57+ maturing NK cell progenies with HCMV-inhibiting activity. Progeny characterization led also to identification of an additional new PB Lin-CD56-CD16+ precursor giving rise to the same CD94/NKG2C+KIR+CD57+ maturing NK cell progenies. Microarray analysis of NK cell progenies revealed a signature compatible with maturing adaptive NK cells. In vivo circulation of multiple common lymphocyte precursors with rapid development to NKG2C+ NK cell progeny is steadily occurring and may thus be a crucial resource for the prompt control of HCMV. We used microarray to compare the transcriptional profiles of human NKG2C+ NK cells derived from i) CD34+DNAM1brightCXCR4+ precursors, ii) Lin-CD34-CD16+CD56- precursors, iii) peripheral blood.
2020-12-31 | GSE136570 | GEO
Project description:Natural Killer cells from cytomegalovirus positive individuals (i.e. adaptive NK) where cultured for seven days with either control antibody, an NKG2C agonist antibody, or an antibody agonist to NKG2C and NKG2A
2019-06-30 | GSE131973 | GEO
Project description:The liver is enriched in innate lymphocytes, including Natural Killer (NK) cells, that can continuously interact with Liver Sinusoidal Endothelial Cells (LSECs) within liver sinusoids. NK cells provide the early defence against infections and malignancies by exerting cytotoxicity and by secreting pro-inflammatory cytokines. To decipher how LSECs affect NK cell phenotype and function, we co-cultured NK cells with LSECs and used microarray technology to identify transcriptomic changes.
2023-07-17 | GSE233222 | GEO
Project description:Characterisation of NKG2C+KIR+ tissue-resident NK cells in human lung and CD49a+ CD56bright NK cells in human blood.
2021-03-24 | GSE166654 | GEO
Project description:Endothelial cell heterogeneity shapes the unique attributes of organ-specific blood vessels; however, how intra-organ vascular cell diversity is established remains unsolved. Liver vascular network is patterned by sinusoidal and hepatocyte co-zonation, however how intra-liver vessels acquire their hierarchical specialized functions is unknown. Here, we resolve the heterogeneity of hepatic vascular cells during development through functional and single-cell RNA sequencing. We show that acquisition of sinusoidal endothelial cell identity is initiated during early development and is completed postnatally, originating from a pool of undifferentiated vascular progenitors at E12. Notably, we identify the peri-natal induction of the transcription factor c-Maf as a critical switch for sinusoidal identity determination. Endothelium-restricted deletion of c-Maf disrupts liver sinusoidal development, aberrantly expands postnatal liver hematopoiesis, promotes excessive postnatal sinusoidal proliferation, and aggravates liver pro-fibrotic sensitivity to chemical insult. Notably, c-Maf overexpression in generic differentiated endothelial cells switches on a liver sinusoidal transcriptional zonation program that maintains hepatocyte function. Therefore, c-Maf represents an inducible intra-organotypic and niche-responsive molecular determinant of sinusoidal cell identity and lays the foundation for designing strategies to initiate vasculature-driven liver repair.
2022-04-02 | GSE174209 | GEO
Project description:Endothelial cell heterogeneity shapes the unique attributes of organ-specific blood vessels; however, how intra-organ vascular cell diversity is established remains unsolved. Liver vascular network is patterned by sinusoidal and hepatocyte co-zonation, however how intra-liver vessels acquire their hierarchical specialized functions is unknown. Here, we resolve the heterogeneity of hepatic vascular cells during development through functional and single-cell RNA sequencing. We show that acquisition of sinusoidal endothelial cell identity is initiated during early development and is completed postnatally, originating from a pool of undifferentiated vascular progenitors at E12. Notably, we identify the peri-natal induction of the transcription factor c-Maf as a critical switch for sinusoidal identity determination. Endothelium-restricted deletion of c-Maf disrupts liver sinusoidal development, aberrantly expands postnatal liver hematopoiesis, promotes excessive postnatal sinusoidal proliferation, and aggravates liver pro-fibrotic sensitivity to chemical insult. Notably, c-Maf overexpression in generic differentiated endothelial cells switches on a liver sinusoidal transcriptional zonation program that maintains hepatocyte function. Therefore, c-Maf represents an inducible intra-organotypic and niche-responsive molecular determinant of sinusoidal cell identity and lays the foundation for designing strategies to initiate vasculature-driven liver repair.
2022-04-02 | GSE174208 | GEO