Netrin-1 directs vascular patterning and maturity in the developing kidney
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1028616 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26400748_1.fastq.gz | Fastqsanger.gz | |||
| SRR26400748_2.fastq.gz | Fastqsanger.gz | |||
| SRR26400749_1.fastq.gz | Fastqsanger.gz | |||
| SRR26400749_2.fastq.gz | Fastqsanger.gz | |||
| SRR26400750_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 18 |
Similar Datasets
Project description:The kidneys intricate vascular system supports body fluid and organ homeostasis. However, little is known about how vascular architecture is established during kidney development. More specifically, how signals from the kidney influence vessel maturity and patterning remains poorly understood. Netrin-1 (Ntn1) is a secreted ligand critical for vessel and neuronal guidance. Here, we demonstrate that Ntn1 is expressed by Foxd1+ stromal progenitors in the developing kidney and conditional deletion (Foxd1GC/+;Ntn1fl/fl) results in hypoplastic kidneys with extended nephrogenesis. Wholemount 3D analyses additionally revealed the loss of a predictable vascular pattern in Foxd1GC/+;Ntn1fl/fl kidneys. As vascular patterning has been linked to vessel maturity, we investigated arterialization. Quantification of the CD31+ endothelium at E15.5 revealed no differences in metrics such as the number of branches or branch points, whereas the arterial vascular smooth muscle metrics were significantly reduced at both E15.5 and P0. In support of our observed phenotypes, whole kidney RNA-seq revealed disruptions to genes and programs associated with stromal cells, vasculature, and differentiating nephrons. Together, our findings highlight the significance of netrin-1 to proper vascularization and kidney development.
2023-10-19 | GSE245506 | GEO
Project description:The intricate vascular system of the kidneys supports body fluid and organ homeostasis. However, little is known about how vascular architecture is established during kidney development. More specifically, how signals from the kidney influence vessel maturity and patterning remains poorly understood. Netrin 1 (Ntn1) is a secreted ligand that is crucial for vessel and neuronal guidance. Here, we demonstrate that Ntn1 is expressed by Foxd1+ stromal progenitors in the developing mouse kidney and conditional deletion (Foxd1GC/+;Ntn1fl/fl) results in hypoplastic kidneys with extended nephrogenesis. Wholemount 3D analyses additionally revealed the loss of a predictable vascular pattern in Foxd1GC/+;Ntn1fl/fl kidneys. As vascular patterning has been linked to vessel maturity, we investigated arterialization. Quantification of the CD31+ endothelium at E15.5 revealed no differences in metrics such as the number of branches or branch points, whereas the arterial vascular smooth muscle metrics were significantly reduced at both E15.5 and P0. In support of our observed phenotypes, whole kidney RNA-seq revealed disruptions to genes and programs associated with stromal cells, vasculature and differentiating nephrons. Together, our findings highlight the significance of Ntn1 to proper vascularization and kidney development.
| S-EPMC10690109 | biostudies-literature
Project description:Blood filtering by the kidney requires the establishment of an intricate vascular system that works to support body fluid and organ homeostasis. Despite these critical roles, little is known about how vascular architecture is established during kidney development. More specifically, how signals from the kidney influence vessel maturity and patterning remains poorly understood. Netrin-1 (Ntn1) is a secreted ligand critical for vessel and neuronal guidance. Here, we demonstrate that Ntn1 is expressed by stromal progenitors in the developing kidney, and conditional deletion of Ntn1 from Foxd1+ stromal progenitors (Foxd1GC/+;Ntn1fl/fl) results in hypoplastic kidneys that display extended nephrogenesis. Despite expression of the netrin-1 receptor Unc5c in the adjacent nephron progenitor niche, Unc5c knockout kidneys develop normally. The netrin-1 receptor Unc5b is expressed by embryonic kidney endothelium and therefore we interrogated the vascular networks of Foxd1GC/+;Ntn1fl/fl kidneys. Wholemount, 3D analyses revealed the loss of a predictable vascular pattern in mutant kidneys. As vascular patterning has been linked to vessel maturity, we investigated arterialization in these mutants. Quantification of the CD31+ endothelium at E15.5 revealed no differences in metrics such as the number of branches or branch points, whereas the arterial vascular smooth muscle metrics were significantly reduced at both E15.5 and P0. In support of these results, whole kidney RNA-seq showed upregulation of angiogenic programs and downregulation of muscle-related programs which included smooth muscle-associated genes. Together, our findings highlight the significance of netrin-1 to proper vascularization and kidney development.
| S-EPMC10153117 | biostudies-literature
Project description:The kidney vasculature has a complex architecture that is essential for renal function. The molecular mechanisms that direct development of kidney blood vessels are poorly characterized. We identified a regionally-restricted, stroma-derived signaling molecule, netrin-1 (Ntn1), as a regulator of renal vascular patterning. Stromal progenitor (SP)-specific ablation of netrin-1 (Ntn1SPKO) resulted in smaller kidneys with fewer glomeruli, as well as profound defects of the renal artery and transient blood flow disruption. Notably, Ntn1 ablation resulted in loss of arterial vascular smooth muscle cell (vSMC) coverage and in ectopic SMC deposition at the kidney surface. This was accompanied by dramatic reduction of arterial tree branching that perdured postnatally. Transcriptomic analysis of Ntn1SPKO kidneys revealed dysregulation of vSMC differentiation, including downregulation of Klf4 which we find expressed in a subset of SPs. Stromal Klf4 deletion similarly resulted in decreased smooth muscle coverage and arterial branching, however without the disruption of renal artery patterning and perfusion seen in Ntn1SPKO. These data suggest a stromal Ntn1-Klf4 axis that regulates stromal differentiation, and reinforce stromal-derived smooth muscle as a key regulator of renal blood vessel formation.
2023-09-10 | GSE242508 | GEO
Project description:Floor plate-derived extracellular signaling molecules, including canonical axon guidance cues of the Netrin family, control neuronal circuit organization. Despite the importance of the floor plate as an essential signaling centre in the developing vertebrate central nervous system, no systematic approach to identify binding partners for floor plate-expressed cellsurface and secreted proteins has been carried out. Here, we used a high-throughput assay to discover extracellular protein-protein interactions, which likely take place in the zebrafish floor plate microenvironment. The assembled floor plate network contains 47 interactions including the hitherto not reported interaction between Netrin-1 and Draxin. We further characterized this interaction, narrowed down the binding interface, and demonstrated that Draxin competes with Netrin receptors for binding to Netrin-1. Our results suggest that Draxin functions as an extracellular Netrin signaling modulator in vertebrates. A reciprocal gradient of Draxin might shape or sharpen the active Netrin gradient, thereby critically modulating its effect.
2015-05-31 | E-MTAB-3609 | biostudies-arrayexpress
Project description:Transcriptional remodeling by OTX2 directs specification and patterning of mammalian definitive endoderm.
| PRJNA1242889 | ENA
Project description:Transcriptional remodeling by OTX2 directs specification and patterning of mammalian definitive endoderm [scRNA_PS_Meso]
| PRJNA1242974 | ENA
Project description:Transcriptional remodeling by OTX2 directs specification and patterning of mammalian definitive endoderm [PS_CUTnRUN]
| PRJNA1250433 | ENA
Project description:Transcriptional remodeling by OTX2 directs specification and patterning of mammalian definitive endoderm [CUTnTAG]
| PRJNA1250439 | ENA
Project description:The generation of induced pluripotent stem (iPS) cells holds great promise in regenerative medicine. However, the relative flaws in the understanding of the molecular mechanisms promoting or limiting reprogramming still hinder the efficient generation of high quality iPS cells. Whereas modulation of the initial Oct4, Sox2, Klf4 and c-Myc (OSKM) cocktail with new transcription factors has been extensively documented, comparatively little is known about soluble molecules promoting the process, even if such recombinant factors could be highly valuable for therapeutic applications. In this study we developed a large-scale identification method to uncover novel programmed cell death (PCD)-related mechanisms limiting somatic cell reprogramming to pluripotency (SCRP). We identified Netrin-1 and its dependence receptor Dcc (Deleted in Colorectal Carcinoma), previously described for their respective survival/death functions both in normal and oncogenic contexts, as novel key SCRP modulators. We show that the early phase of SCRP is accompanied with a strong Netrin-1 deficiency, due to the improper epigenetic regulation of the Ntn1 promoter by OSKM. Mechanistically, we demonstrate that such Netrin-1 imbalance induces apoptosis mediated by the dependence receptor Dcc in a p53-independent manner. Correction of the Netrin-1/Dcc equilibrium by gain-of-ligand and loss-of-receptor experiments constrains apoptosis and improves reprogramming. As a consequence, we propose a novel iPS derivation protocol including a sequential treatment with recombinant Netrin1 that greatly facilitates the generation of mouse and human iPS cells. RNA-sequencing of mouse embryonic fibroblasts (passage 2 and passage 4), mouse pre-iPS cells (passage 5 and passage 25), 1 clone of control iPS (passage 5 and passage 25) and 2 independent clones of "Netrin-1 derived" iPS cells (passage 5 and passage 25). For this analysis, mouse iPS cell lines were grown in KSR+LIF media.
2015-09-01 | E-GEOD-54107 | biostudies-arrayexpress