Microenvironmental Control of Hematopoietic Niche Capacity via CXCL8 and Protein Kinase C
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA789478 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17247448_1.fastq.gz | Fastqsanger.gz | |||
| SRR17247448_2.fastq.gz | Fastqsanger.gz | |||
| SRR17247449_1.fastq.gz | Fastqsanger.gz | |||
| SRR17247449_2.fastq.gz | Fastqsanger.gz | |||
| SRR17247450_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 62 |
Similar Datasets
Project description:Altered hematopoietic stem cell (HSC) fate underlies primary blood disorders but microenvironmental factors controlling HSC fate are poorly understood. Genetically barcoded GESTALT zebrafish were used to screen for factors expressed by the sinusoidal vascular niche that alter the phylogenetic distribution of the HSC pool under native conditions. Dysregulated expression of protein kinase C delta (PKC-d, encoded by prkcda) increased the number of HSC clones by approximately 50% and expanded polyclonal populations of immature neutrophil and erythroid precursors. PKC agonists such as cxcl8 augmented HSC competition for residency within the niche and expanded defined niche populations. Cxcl8 induced association of PKC-d with the focal adhesion complex, activating MEK/ERK signaling and expression of niche factors in human endothelial cells. Our findings demonstrate the existence of reserve capacity within the niche which is controlled by PKC and has significant impact on HSC phylogenetic and phenotypic fate.
2023-05-15 | GSE191029 | GEO
Project description:The microenvironment is an important regulator of hematopoietic stem and progenitor cell (HSPC) biology. Interactions between the niche and stem cells have been difficult to track, but recent advances marking fluorescent HSPCs have allowed exquisite visualization in the caudal hematopoietic tissue (CHT) of the developing zebrafish. Sinusoidal endothelial cells interact closely with HSPCs as they colonize this niche. Here we show that the chemokine cxcl8 and its receptor, cxcr1, are abundantly expressed by zebrafish endothelial cells and we identify cxcl8/cxcr1 signaling as a positive regulator of HSPC colonization using genetic gain- and loss-of-function techniques. Single-cell tracking experiments demonstrated that this effect is due to an increase in HSPC “cuddling” by endothelial cells, thereby increasing CHT residency time and allowing more HSPC cell divisions to occur. Enhanced cxcl8/cxcr1 signaling was associated with an increase in the volume of the CHT and induction of cxcl12a expression, favoring HSPC colonization. Finally, using parabiotic zebrafish, we show that cxcr1 acts stem cell non-autonomously to improve the efficiency of donor HSPC engraftment. This work identifies a mechanism by which the hematopoietic niche remodels to promote HSPC engraftment and suggests that cxcl8/cxcr1 signaling is a potential therapeutic target in patients undergoing hematopoietic stem cell transplantation.
2017-03-24 | GSE92541 | GEO
Project description:The microenvironment is an important regulator of hematopoietic stem and progenitor cell (HSPC) biology. Interactions between the niche and stem cells have been difficult to track, but recent advances marking fluorescent HSPCs have allowed exquisite visualization in the caudal hematopoietic tissue (CHT) of the developing zebrafish. Sinusoidal endothelial cells interact closely with HSPCs as they colonize this niche. Here we show that the chemokine cxcl8 and its receptor, cxcr1, are abundantly expressed by zebrafish endothelial cells and we identify cxcl8/cxcr1 signaling as a positive regulator of HSPC colonization using genetic gain- and loss-of-function techniques. Single-cell tracking experiments demonstrated that this effect is due to an increase in HSPC “cuddling” by endothelial cells, thereby increasing CHT residency time and allowing more HSPC cell divisions to occur. Enhanced cxcl8/cxcr1 signaling was associated with an increase in the volume of the CHT and induction of cxcl12a expression, favoring HSPC colonization. Finally, using parabiotic zebrafish, we show that cxcr1 acts stem cell non-autonomously to improve the efficiency of donor HSPC engraftment. This work identifies a mechanism by which the hematopoietic niche remodels to promote HSPC engraftment and suggests that cxcl8/cxcr1 signaling is a potential therapeutic target in patients undergoing hematopoietic stem cell transplantation.
2017-03-24 | GSE92542 | GEO
Project description:BMX Kinase Mediates Gilteritinib Resistance in FLT3-mutated AML through Microenvironmental Factors
| PRJNA819410 | ENA
Project description:Altered hematopoietic stem cell (HSC) fate underlies primary blood disorders but microenvironmental factors controlling this are poorly understood. Genetically barcoded genome editing of synthetic target arrays for lineage tracing (GESTALT) zebrafish were used to screen for factors expressed by the sinusoidal vascular niche that alter the phylogenetic distribution of the HSC pool under native conditions. Dysregulated expression of protein kinase C delta (PKC-δ, encoded by prkcda) increases the number of HSC clones by up to 80% and expands polyclonal populations of immature neutrophil and erythroid precursors. PKC agonists such as cxcl8 augment HSC competition for residency within the niche and expand defined niche populations. CXCL8 induces association of PKC-δ with the focal adhesion complex, activating extracellular signal-regulated kinase (ERK) signaling and expression of niche factors in human endothelial cells. Our findings demonstrate the existence of reserve capacity within the niche that is controlled by CXCL8 and PKC and has significant impact on HSC phylogenetic and phenotypic fate.
| S-EPMC10824047 | biostudies-literature
Project description:An unanticipated feature of the human neonatal CD4 T cell response is a robust capacity to produce CXCL8. However, this 'innate-like' function dissipates with age and is scarce in the adult. Here, we investigated the fate of CD4+CXCL8+ cells and their transition into conventional adaptive T cells. We show that CXCL8 is imprinted on immature thymocytes prior to TCR signalling and is maintained in T cell committed thymic progenitors and recent thymic emigrants (RTEs) of adults as well as neonates. Hence, rather than being unique to neonates, CXCL8-producing CD4+ T cells decrease with age in humans (and in humanised mice) owing to the decline in thymic output, coupled with the cells’ peripheral expansion. By cloning of CXCL8+CD4+ cells from cord blood, we were able to track effector function within daughter cells and demonstrate that these cells can convert to IFN-g producing cells. In sum, we provide direct evidence that ‘innate like’ CXCL8-producing CD4+ T cells emerge from the thymus and can transition into conventional adaptive Th1 cells
2017-08-09 | GSE84686 | GEO
Project description:To determine the functional significance of the expression of CXCL8 in mesenchymal GSCs, we examined the effect of CXCL8 disruption with two non-overlapping small hairpin RNAs (shRNA) on the mesenchymal GSC maintenance. Silencing CXCL8 with two independent shRNAs significantly reduced CXCL8 expression on in mesenchymal GSCs (839 and 2907) .
2023-06-27 | GSE214248 | GEO
Project description:CXCL8 and CXCR1 Remodel the Vascular Niche to Promote Hematopoietic Stem and Progenitor Cell Colonization and Engraftment
| PRJNA358001 | ENA
Project description:Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) is a distinct entity that has conspicuously tumor microenvironment compared with EBV-negative gastric carcinoma. However, the exact role of EBV in gastric carcinogenesis remains elusive. In the present study, we found that EBV upregulated CXCL8 expression, and CXCL8 significantly promoted vasculogenic mimicry (VM) formation of gastric carcinoma cells. In accordance with these observations, CXCL8 increased cell proliferation and migration of AGS and BGC823 cells, respectively. In addition, activation of NF-κB signaling was involved in VM formation induced by CXCL8, which was blocked by NF-κB inhibitor BAY 11-7082. Furthermore, EBV encoded lncRNA RPMS1 activated the NF-κB signaling cascade, which is responsible for EBV-induced VM formation. Both xenografts and clinical samples of EBVaGC exhibit VM histologically, which are correlated with CXCL8 over-expression. Finally, CXCL8 is positively correlated with overall survival in gastric carcinoma patients. In conclusion, EBV-upregulated CXCL8 expression promotes VM formation in gastric carcinoma via NF-κB signaling and CXCL8 may serve as a novel anti-tumor target for EBVaGC.
2021-10-14 | GSE185627 | GEO
Project description:Residence of cancer-propagating cells (CPCs) within preferential microenvironmental niches has a major part in evading therapy. However, the nature of niches involved and the mechanisms protecting CPCs remain largely unknown. We addressed these issues in mouse transplantation models of acute lymphoblastic leukemia (ALL). When the engrafted leukemic cells substantially damaged adjacent vascular structures and endosteal linings in the bone marrow (BM), after chemotherapy small foci of CPCs were retained, surrounded by sheaths of supporting cells that comprise a novel niche. We investigated patients’ BM biopsies and found evidence of a similar process in patients receiving induction-therapy. The efficacy of chemotherapy was enhanced by interfering with the niche formation or niche-CPC interaction. We therefore identified a therapy-induced niche that protects CPCs. We used microarrays to compare the gene expression profile of ALL cell line (Nalm-6) from model (A0D) mice and rediduel cells from Ara-C treatment for 2 days (A2D) mice. Engrafted NALM-6-GFP+ cells from A0D mice and residual cells from A2D mice were flow sorted. Total RNA was isolated using RNeasy micro kit (Qiagen). Biotinylated cRNA was hybridized using HGU133Plus 2.0 GeneChip arrays (Affymetrix).
2014-04-21 | E-GEOD-56273 | biostudies-arrayexpress