Embryo-derived chemokine CXCL12 enhances the pregnancy outcome via improved endometrial receptivity
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA644913 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12174602.fastq.gz | Fastqsanger.gz | |||
| SRR12174603.fastq.gz | Fastqsanger.gz | |||
| SRR12174604.fastq.gz | Fastqsanger.gz | |||
| SRR12174605.fastq.gz | Fastqsanger.gz | |||
| SRR12174606.fastq.gz | Fastqsanger.gz |
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Project description:Intrauterine infusion of CXCL12 has a beneficial effect on endometrial angiogenesis by recontruction of endometrial vasculature and improvement of endometrial receptivity
2020-07-09 | GSE154039 | GEO
Project description:Successful pregnancy inevitably depends on the implantation of a competent embryo into a receptive endometrium. Although many substances have been suggested to improve the rate of embryo implantation targeting enhancement of endometrial receptivity, currently there rarely are effective evidence-based treatments to prevent or cure this condition. Here we strongly suggest minimally-invasive intra-uterine administration of embryo-secreted chemokine CXCL12 as an effective therapeutic intervention. Chemokine CXCL12 derived from pre- and peri-implanting embryos significantly enhances the rates of embryo attachment and promoted endothelial vessel formation and sprouting in vitro. Consistently, intra-uterine CXCL12 administration in C57BL/6 mice improved endometrial receptivity showing increased integrin β3 and its ligand osteopontin, and induced endometrial angiogenesis displaying increased numbers of vessel formation near the lining of endometrial epithelial layer with higher CD31 and CD34 expression. Furthermore, intra-uterine CXCL12 application dramatically promoted the rates of embryo implantation with no morphologically retarded embryos. Thus, our present study provides a novel evidence that improved uterine endometrial receptivity and enhanced angiogenesis induced by embryo-derived chemokine CXCL12 may aid to develop a minimally-invasive therapeutic strategy for clinical treatment or supplement for the patients with repeated implantation failure with less risk.
| S-EPMC8016928 | biostudies-literature
Project description:Beyond its thermogenic potential, brown adipose tissue (BAT) performs important endocrine functions that regulate metabolism. However, the BAT microenvironment and the factors involved in BAT homeostasis and adaptation to cold remain poorly characterized. We therefore aimed to study secreted factors from active brown adipocytes that may be involved in adipocyte function and/or may orchestrate inter-cellular communications. For this, mRNA levels in mature adipocytes of brown, beige and white adipose depots from mice exposed to 21 days of cold were evaluated using RNA sequencing, and bioinformatic analysis was used to predict for potentially secreted factors. Cxcl12 was found to be the most cold-induced C-X-C chemokine in BAT, and Cxcl12 mRNA expression analysis by qPCR and fluorescence in-situ hybridization revealed its enrichment in brown adipocytes upon cold. Cold increased CXCL12 secretion from BAT, yet its level in plasma remained unchanged indicating a potential local action. Cxcl12 knockdown in mature brown adipocytes impaired thermogenesis, estimated by norepinephrine (NE)-induced Ucp1 gene expression, glycerol release and mitochondrial respiration despite unaltered β-adrenergic signaling, suggesting Cxcl12 regulates adipocyte function independently from the β-adrenergic pathway. Importantly, unaltered adipocyte characteristics upon Cxcl12 loss may indicate CXCL12 primarily regulates the NE-induced adipocyte activation. Furthermore, CXCL12 might exert inter-cellular crosstalk via its capacity to promote macrophage chemotaxis and neurite outgrowth. Here we present CXCL12 as a novel brown adipocyte, cold-induced secreted factor involved in adipocyte function and inter-cellular crosstalk within BAT.
2025-02-12 | GSE242711 | GEO
Project description:Nathaniel L. Coggins, Danielle Trakimas, S. Laura Chang, Anna Ehrlich, Paramita Ray, Kathryn E. Luker, Jennifer J. Linderman & Gary D. Luker. CXCR7 controls competition for recruitment of β-arrestin 2 in cells expressing both CXCR4 and CXCR7. PLoS ONE 9, 6 (2014).
Chemokine CXCL12 promotes growth and metastasis of more than 20 different human cancers, as well as pathogenesis of other common diseases. CXCL12 binds two different receptors, CXCR4 and CXCR7, both of which recruit and signal through the cytosolic adapter protein β-arrestin 2. Differences in CXCL12-dependent recruitment of β-arrestin 2 in cells expressing one or both receptors remain poorly defined. To quantitatively investigate parameters controlling association of β-arrestin 2 with CXCR4 or CXCR7 in cells co-expressing both receptors, we used a systems biology approach combining real-time, multi-spectral luciferase complementation imaging with computational modeling. Cells expressing only CXCR4 maintain low basal association with β-arrestin 2, and CXCL12 induces a rapid, transient increase in this interaction. In contrast, cells expressing only CXCR7 have higher basal association with β-arrestin 2 and exhibit more gradual, prolonged recruitment of β-arrestin 2 in response to CXCL12. We developed and fit a data-driven computational model for association of either CXCR4 or CXCR7 with β-arrestin 2 in cells expressing only one type of receptor. We then experimentally validated model predictions that co-expression of CXCR4 and CXCR7 on the same cell substantially decreases both the magnitude and duration of CXCL12-regulated recruitment of β-arrestin 2 to CXCR4. Co-expression of both receptors on the same cell only minimally alters recruitment of β-arrestin 2 to CXCR7. In silico experiments also identified β-arrestin 2 as a limiting factor in cells expressing both receptors, establishing that CXCR7 wins the "competition" with CXCR4 for CXCL12 and recruitment of β-arrestin 2. These results reveal how competition for β-arrestin 2 controls integrated responses to CXCL12 in cells expressing both CXCR4 and CXCR7. These results advance understanding of normal and pathologic functions of CXCL12, which is critical for developing effective strategies to target these pathways therapeutically.
2024-09-02 | BIOMD0000000599 | BioModels
Project description:Stromal fibroblasts reside in inflammatory tissues that are characterized by either immune suppression or activation. Whether and how fibroblasts adapt to these contrasting microenvironments remains unknown. Cancer-associated fibroblasts (CAFs) mediate immune quiescence by producing the chemokine CXCL12, which coats cancer cells to suppress T cell infiltration. We examined whether CAFs can also adopt an immune-promoting chemokine profile. Single-cell RNA-sequencing of CAFs from mouse pancreatic adenocarcinomas identified a sub-population of CAFs with decreased expression of CXCL12 and increased expression of the T cell-attracting chemokine, CXCL9 in association with T cell infiltration. TNFa and IFNg containing conditioned media from activated CD8+ T cells converted stromal fibroblasts from a CXCL12+/CXCL9- immune suppressive phenotype into a CXCL12-/CXCL9+ immune-activating phenotype. Recombinant IFNg and TNFa acted synergistically to induce CXCL9 expression, whereas TNFa alone suppressed CXCL12 expression. This coordinated chemokine switch leads to increased T cell infiltration in an in vitro chemotaxis assay. Our study demonstrates that CAFs have a phenotypic plasticity that allows their adaptation to contrasting immune tissue microenvironments.
2023-04-03 | GSE228835 | GEO
Project description:Stromal fibroblasts reside in inflammatory tissues that are characterized by either immune suppression or activation. Whether and how fibroblasts adapt to these contrasting microenvironments remains unknown. Cancer-associated fibroblasts (CAFs) mediate immune quiescence by producing the chemokine CXCL12, which coats cancer cells to suppress T cell infiltration. We examined whether CAFs can also adopt an immune-promoting chemokine profile. Single-cell RNA-sequencing of CAFs from mouse pancreatic adenocarcinomas identified a sub-population of CAFs with decreased expression of CXCL12 and increased expression of the T cell-attracting chemokine, CXCL9 in association with T cell infiltration. TNFa and IFNg containing conditioned media from activated CD8+ T cells converted stromal fibroblasts from a CXCL12+/CXCL9- immune suppressive phenotype into a CXCL12-/CXCL9+ immune-activating phenotype. Recombinant IFNg and TNFa acted synergistically to induce CXCL9 expression, whereas TNFa alone suppressed CXCL12 expression. This coordinated chemokine switch leads to increased T cell infiltration in an in vitro chemotaxis assay. Our study demonstrates that CAFs have a phenotypic plasticity that allows their adaptation to contrasting immune tissue microenvironments.
2023-04-03 | GSE228836 | GEO
Project description:The chemokine CXCL12 and its receptor CXCR4 play important roles in signaling and migration of T-cells, but little is known about the transcriptional events involved in CXCL12-mediated T-cell migration. In this study we performed microarray analysis on CXCL12- treated T-cells, and found that the Wnt family of proteins was significantly upregulated during CXCL12 treatment. Confirmation of these results by real-time PCR and Western analysis indicated that the non-canonical Wnt pathway was specifically upregulated during CXCL12 treatment. In vitro and in vivo knockdown studies confirm that b-catenin (the key mediator of canonical Wnt signaling) is not involved in the CXCL12-mediated migration of T-cells. However, Wnt5A, a non-canonical Wnt protein, increases signaling through the CXCL12/ CXCR4 axis via Protein Kinase C (PKC). Our results demonstrated that CXCL12 required Wnt5A to mediate T-cell migration, and the treatment of T-cells with recombinant Wnt5A sensitized T-cells to CXCL12 induced migration. Additionally, Wnt5A expression was required for the sustained expression of CXCR4, both transcriptionally and translationally. These results could be translated in vivo, using EL4 thymoma metastasis as a model of T-cell migration. Taken together our data indicate, for the first time, that Wnt5A is a critical mediator of the CXCL12/ CXCR4 signaling axis. Keywords: Wnt5A, CXCL12, CXCL12, CXCR4, T-cell Migration
2009-01-01 | GSE12449 | GEO
Project description:The chemokine CXCL12 and its receptor CXCR4 play important roles in signaling and migration of T-cells, but little is known about the transcriptional events involved in CXCL12-mediated T-cell migration. In this study we performed microarray analysis on CXCL12- treated T-cells, and found that the Wnt family of proteins was significantly upregulated during CXCL12 treatment. Confirmation of these results by real-time PCR and Western analysis indicated that the non-canonical Wnt pathway was specifically upregulated during CXCL12 treatment. In vitro and in vivo knockdown studies confirm that b-catenin (the key mediator of canonical Wnt signaling) is not involved in the CXCL12-mediated migration of T-cells. However, Wnt5A, a non-canonical Wnt protein, increases signaling through the CXCL12/ CXCR4 axis via Protein Kinase C (PKC). Our results demonstrated that CXCL12 required Wnt5A to mediate T-cell migration, and the treatment of T-cells with recombinant Wnt5A sensitized T-cells to CXCL12 induced migration. Additionally, Wnt5A expression was required for the sustained expression of CXCR4, both transcriptionally and translationally. These results could be translated in vivo, using EL4 thymoma metastasis as a model of T-cell migration. Taken together our data indicate, for the first time, that Wnt5A is a critical mediator of the CXCL12/ CXCR4 signaling axis. Experiment Overall Design: Primary T cells were treated with human CXCL12 (Peprotech, Rocky Hill, NJ) at 100 ng/ml per 10 million cells overnight in a humidified incubator at 37ºC with 5% CO2. Control cells were incubated in media only. Cells were harvested and washed with ice cold PBS for 2 times followed by the addition of ice cold TRIzol (Invitrogen, Carlsbad, CA) and frozen at -80ºC overnight. Total RNA was isolated using the RNA isolation kit manufactured by Qiagen (Valencia, CA). The cDNA was prepared from equal amount of RNA using a cDNA preparation kit (Bio-Rad, Hercules, CA) followed by preparation of cRNA according to manufacturerâs instructions (Agilent, Santa Clara, CA). The cRNA was amplified and labeled with either Cy-3 or Cy-5, using the Agilent low-input linear amplification kit, according to manufacturerâs protocols. Labeled cRNA were applied to the Human 44K whole genome oligo array slides (Agilent, Santa Clara, CA). Slides were hybridized in a rotating chamber overnight at 60ºC in 6X SSC. Next day, slides were washed with 0.005% Triton X-102 for 10 minutes, and then in 0.1X SSC, 0.005% Triton X-102 for 5 minutes on ice. Slides were dried using a nitrogen-filled air gun, and scanned using an Agilent scanner. Images were analyzed using the Agilent Feature Extractor Software, Version A.7.5.1 and ratios for each spot were calculated.
2009-01-14 | E-GEOD-12449 | biostudies-arrayexpress
Project description:T-acute lymphoblastic leukaemia (T-ALL) is an aggressive haematological malignancy, which comprises the accumulation of malignant T-cell precursors. Despite current therapies, up to 20% of children with failure to respond to treatments and relapse. Our understanding of T-ALL infiltration and how leukaemia cells-microenvironment interactions play a role in the clinical outcome is still vague. In the present study, we showed a novel function of the chemokine CXCL12, which induced fast epigenetic changes within minutes in cell lines and primary T-ALL cells. Our results identified that CXCL12-mediated H3K9 methylation impacted on the global chromatin configuration and the nuclear mechanics of T-ALL cells. We characterised changes in the transcriptional profile of T-ALL cells associated with rapid CXCL12 stimulation. We demonstrated that cytoskeletal changes and protein kinase-C (PKC) activity were the molecular mechanisms by which CXCL12 promoted H3K9 methylation in T-ALL cells. Furthermore, targeting H3K9 methyltransferases reduced the migration and the nuclear deformability in both cell line and primary human ALL cells. Together, our data indicate a novel funcion of H3K9 methylation induced by CXCL12 in T-ALL cells, that reveals the significance of nuclear changes to mechanobiology and function of leukemia cells and emerges as a promising pharmacological target against T-ALL infiltration and dissemination.
2021-01-31 | GSE162605 | GEO
Project description:The periodontal ligament (PDL) is one of the connective tissues located between the tooth and bone. It is characterized by rapid turnover. Periodontal ligament fibroblasts (PDLFs) play major roles in the rapid turnover of the PDL. Microarray analysis of human PDLFs (HPDLFs) and human dermal fibroblasts (HDFs) revealed markedly high expression of chemokine (CXC motif) ligand 12 (CXCL12) in the HPDLFs, which plays an important role in the migration of mesenchymal stem cells (MSCs). The function of CXCL12 in the periodontal ligament was investigated in HPDLFs. CXCL12 in HPDLFs and HDFs was examined by microarray, RT-PCR, qRT-PCR and ELISA. It was also immunohistochemically examined in the PDL in vivo. Chemotactic ability of CXCL12 was evaluated both in PDLFs and HDFs with migration assay of MSCs. The expression of CXCL12 in the HPDLFs was much higher than that in HDFs in vitro. CXCL12 was localized in fibroblasts and extracellular matrix in the PDL in rats. Migration assay demonstrated that the number of migrated MSCs by HPDLFs was significantly higher than that by HDFs. In addition, the migrated MSCs also expressed CXCL12 and several genes that are familiar to fibroblasts. The results suggested that PDLFs are able to synthesize and secrete CXCL12 protein, and that CXCL12 induces migration of MSCs in the PDL in order to maintain rapid turnover of the PDL. The objective of this study was to investigate the function of CXCL12 in the PDL with rapid turnover.Microarray analysis was performed using a Whole Human Genome 8x60K (Agilent Technologies, Tokyo, Japan) containing approximately 44,000 transcripts. According to the manufacturerM-bM-^@M-^Ys protocol, total RNAs from HPDLFs and HDFs were labeled with Cy3 and hybridized on the microarray. The hybridization data for HPDLFs were compared with data for HDFs.
2013-11-07 | E-GEOD-52162 | biostudies-arrayexpress