Endocardium-to-coronary artery differentiation during heart development and regeneration involves sequential roles of Bmp2 and Cxcl12/Cxcr4.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA887779 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR21831555_1.fastq.gz | Fastqsanger.gz | |||
| SRR21831555_2.fastq.gz | Fastqsanger.gz | |||
| SRR21831556_1.fastq.gz | Fastqsanger.gz | |||
| SRR21831556_2.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 4 of 4 |
Similar Datasets
Project description:Endocardial cells lining the heart lumen are coronary vessel progenitors during embryogenesis. Re-igniting this developmental process in adults could regenerate blood vessels lost during cardiac injury, but this requires additional knowledge on molecular regulators. Here, we use mouse genetics and scRNAseq to identify novel regulators of endocardial angiogenesis and precisely assess the role of CXCL12/CXCR4 signaling. Time-specific lineage tracing demonstrated that endocardial cells differentiated in coronary endothelial cells primarily at mid-gestation. A new mouse line reporting CXCR4 activity—along with cell-specific gene deletions—revealed it was specifically required for artery morphogenesis rather than angiogenesis. Integrating scRNAseq data of endocardial-derived coronary vessels from mid- and late-gestation identified a Bmp2-expressing transitioning population specific to mid-gestation. Bmp2 stimulated endocardial angiogenesis in vitro and in injured neonatal mouse hearts. Our data shed light on how understanding the molecular mechanisms underlying endocardial angiogenesis can identify new potential therapeutic targets promoting revascularization of the injured heart.
2022-10-09 | GSE214942 | GEO
Project description:Endocardial cells lining the heart lumen are coronary vessel progenitors during embryogenesis. Re-igniting this developmental process in adults could regenerate blood vessels lost during cardiac injury, but this requires additional knowledge of molecular mechanisms. Here, we use mouse genetics and scRNA-seq to identify regulators of endocardial angiogenesis and precisely assess the role of CXCL12/CXCR4 signaling. Time-specific lineage tracing demonstrated that endocardial cells differentiated into coronary endothelial cells primarily at mid-gestation. A new mouse line reporting CXCR4 activity-along with cell-specific gene deletions-demonstrated it was specifically required for artery morphogenesis rather than angiogenesis. Integrating scRNA-seq data of endocardial-derived coronary vessels from mid- and late-gestation identified a Bmp2-expressing transitioning population specific to mid-gestation. Bmp2 stimulated endocardial angiogenesis in vitro and in injured neonatal mouse hearts. Our data demonstrate how understanding the molecular mechanisms underlying endocardial angiogenesis can identify new potential therapeutic targets promoting revascularization of the injured heart.
| S-EPMC9833645 | biostudies-literature
Project description:Gene expression analysis in senescent HeLa cells to examine the differential CXCL12-CXCR4 signalling pathways.
2025-03-18 | GSE254769 | GEO
Project description:Bmp2 and Notch cooperate to pattern the embryonic endocardium
| PRJNA413427 | ENA
Project description:CXCL12-CXCR4 signalling axis in cellular senescence
| PRJNA1071660 | ENA
Project description:T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy characterized by infiltration of the bone marrow and other sites with transformed T cell progenitors. The role of tissue microenvironments in the pathogenesis of T-ALL or any other type of acute leukemia is little understood. In delineating interactions between T-ALL cells and their environment, we initially found that T-ALL cells express high surface levels of the chemokine receptor CXCR4. Intravital imaging of an intact tibia revealed T-ALL cells in direct contact with bone marrow stromal cells producing the CXCR4 ligand, CXCL12. Genetic targeting of CXCR4 on T-ALL cells resulted in a marked reduction of leukemia burden and prolonged disease remission, and disruption of the CXCL12/CXCR4 axis using small molecule inhibitors prevented T-ALL progression in a primary xenograft model. Finally, we were able to show that CXCR4 inhibition significantly decreased expression of Myc and its target genes. Myc expression is a key regulator of T-ALL leukemia initiating cell (LIC) activity, suggesting that CXCR4 inhibition can suppress LIC activity by silencing the Myc response in T-ALL cells. Our data suggest that targeting of CXCL12/CXCR4 signaling could be a powerful new tool for combating T-ALL, a disease with no current targeted therapies. Mouse T-ALL cells were treated ex vivo with Cxcr4 inhibitor AMD3100 or vehicle control. Additionally, mouse T-ALL primary tumors were isolated from control (Cxcr4+/+) or knockout (Cxcr4-/-) animals. Total RNA was extracted from samples using the RNeasy Plus Mini Kit (Qiagen). Samples were then subject to PolyA selection using oligo-dT beads (Life Technologies, Carlsbad, CA) according to the manufacturer's instructions. The resulting RNA samples were then used as input for library construction using the dUTP method as described by Parkhomchuck et al., 2009. RNA libraries were then sequenced on the Illumina HiSeq 2500 using 50bp single-end reads.
2015-08-12 | E-GEOD-60367 | biostudies-arrayexpress
Project description:Pancreatic cancer (PaCa) has one of the poorest prognoses among gastrointestinal cancers because of rapid development of treatment resistance, which renders chemotherapy and radiotherapy no longer effective. As the mechanism by which PaCa becomes resistant to radiotherapy is unknown, we established radiation-resistant PaCa cell lines to investigate the factors involved in radiation resistance. We investigated the role of the C-X-C motif chemokine 12 (CXCL12)/ C-X-C chemokine receptor type 4 (CXCR4) axis in radiation resistance in PaCa and the effect of a CXCR4 antagonist on radiation-resistant PaCa cell lines. As confirmed by immunofluorescence staining, RT-qPCR, and Western blotting, the expression of CXCR4 was higher in the radiation-resistant PaCa cell lines than in normal PaCa cell lines. The invasion ability of radiation-resistant PaCa cell lines was greater than that of normal cell lines and was enhanced by CXCL12 treatment and co-culture with fibroblasts; this enhanced invasion ability was suppressed by the CXCR4 antagonist AMD070. Irradiation after treatment with the CXCR4 antagonist suppressed the colonization of radiation-resistant PaCa cell lines. In conclusion, the CXCL12/CXCR4 axis may be involved in the radiation resistance of PaCa. We believe this result will help develop treatments for PaCa.
2022-01-14 | GSE193616 | GEO
Project description:T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy characterized by infiltration of the bone marrow and other sites with transformed T cell progenitors. The role of tissue microenvironments in the pathogenesis of T-ALL or any other type of acute leukemia is little understood. In delineating interactions between T-ALL cells and their environment, we initially found that T-ALL cells express high surface levels of the chemokine receptor CXCR4. Intravital imaging of an intact tibia revealed T-ALL cells in direct contact with bone marrow stromal cells producing the CXCR4 ligand, CXCL12. Genetic targeting of CXCR4 on T-ALL cells resulted in a marked reduction of leukemia burden and prolonged disease remission, and disruption of the CXCL12/CXCR4 axis using small molecule inhibitors prevented T-ALL progression in a primary xenograft model. Finally, we were able to show that CXCR4 inhibition significantly decreased expression of Myc and its target genes. Myc expression is a key regulator of T-ALL leukemia initiating cell (LIC) activity, suggesting that CXCR4 inhibition can suppress LIC activity by silencing the Myc response in T-ALL cells. Our data suggest that targeting of CXCL12/CXCR4 signaling could be a powerful new tool for combating T-ALL, a disease with no current targeted therapies.
2015-08-12 | GSE60367 | GEO
Project description:Analysis of genes in DNA damage induced senescence using BrdU as a DNA damaging agent in HeLa cells which can trigger cellular senescence and identifying effect of CXCL12-CXCR4 axis during this process.
2017-12-30 | GSE93568 | GEO
Project description:CXCR4 cDNA transcripts were subcloned into plenti-IRES-GFP vectors, and stably transduced using a lentiviral system In addition to wild-type CXCR4, vectors with the mutations c.1013C>G (p.Ser338*), c.932_933insT (p.Thr311fs), and c.1030_1041delinsGT (p.Ser344fs) were generated. Cell lines were stimulated with 50nM of the CXCR4 ligand CXCL12 (SDF1A) (R&D Systems, Minneapolis MN) for two hours. RNA from each sample was extracted at baseline and at 2 hours. At baseline and following stimulation, RNA was extracted and processed for analysis using Affymetrix Human Gene ST 2.0 arrays (Affymetrix, Santa Clara, CA). Data was analyzed using Oligo and Limma bioconductor packages in R using TMM normalization.
2016-06-10 | E-GEOD-83150 | biostudies-arrayexpress