Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Plexin-B2 regulates mechanotension during multicellular organization

ABSTRACT: During multicellular organization, individual cells need to constantly adjust intracellular contractility and junctional adhesive properties in order to maintain tissue cohesion and mechanotension. The membrane receptors linking external biochemical cues and internal cell mechanics are incompletely understood. Here, we reveal that the axon guidance receptor Plexin-B2 regulates intracellular mechanotension, and this in turn impacts cell-cell/cell-matrix adhesiveness during self-assembly of human embryonic stem cells (hESCs) and neuroprogenitor cells (hNPCs) into epithelial structures. The altered tissue mechanics caused by Plexin-B2 deficiency or over expression affects stem cell behaviors as well as β-catenin and YAP mechanosensing. Strikingly, Plexin-B2 deficiency results in accelerated neuronal differentiation, while proper levels of Plexin-B2 activity are required for maintaining cytoarchitectural integrity of the neuroepithelium as modeled in cerebral organoids. Mechanistically, Plexin-B2 engages its extracellular and Ras-GAP domains for mechanoregulation via RAP1/2. Our studies establish mechanoregulation as a key function of Plexin-B2 during multicellular organization, thereby solidifying the principle of force- mediated regulation of stem cell biology and tissue morphogenesis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE158017 | GEO | 2021/09/07

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Plexin-B2 reduces glioma cell cohesion and regulates glioma-vascular interactions

Project description:The diffuse invasion of glioblastoma (GBM) cells into healthy brain tissue is a main contributor for the high lethality of this most frequent form of malignant brain tumor. Plexins are cell surface receptors for semaphorins and control cell adhesion and cytoskeletal dynamics in development and in adult physiology. Gene expression of Plexin-B2 is upregulated in GBM and correlates with its lethality. We show here that Plexin-B2 activity can reduce the cohesiveness of GBM cells, which facilitates their invasive capacity. Targeted deletion of Plexin-B2 in GBM cells increased their cohesion to each other, revealing that a major function of Plexin-B2 activity is to downregulate cell-cell adhesion, possibly by downregulating other cell adhesion systems. In an in vivo intracranial transplant model, invasion of Plexin-B2 mutant GBM cells was impaired, with cells invading shorter distances. Interestingly, the loss of Plexin-B2 also changed the migration mode of cells, with the balance of cells in brain stroma vs. capillary space shifted: Plexin-B2 mutant cells were more likely to adhere to the vasculature. Our structure-function analyses revealed that the Ras-GAP domain of Plexin-B2 that is the main functional output responsible for the cohesion regulating function of Plexin-B2. Transcriptomic analyses of Plexin-B2 KO cells suggests that Plexin-B2 loss in different GBM cell lines has no direct transcriptional target genes, however, consistently, cell adhesion molecules were changed in expression, suggesting that cells compensate for loss of Plexin-B2. Thus, Plexin-B2 acts as a key regulator of the cohesiveness of GBM cells, thereby facilitating their invasiveness.

2021-01-13 | GSE126658 | GEO

Plexin-B2 regulates mechanotension during multicellular organization

Project description:Plexin-B2 regulates mechanotension during multicellular organization

| PRJNA663651 | ENA

Microglia and macrophages promote corralling, wound compaction and recovery in spinal cord injury via Plexin-B2

Project description:Tissue repair after spinal cord injury (SCI) requires mobilization of immune and glial cells to form a protective barrier that seals the wound and facilitates debris clearing, inflammatory containment, and matrix compaction. This process involves corralling, wherein phagocytic immune cells become confined to the necrotic core surrounded by an astrocytic border. Here, we elucidate a temporally distinct gene signature in injury-activated microglia/macrophages (IAM), which engages axon guidance pathways. Plexin-B2 is upregulated in IAM, which is required for motosensory recovery after SCI. Plexin-B2 deletion in myeloid cells impairs corralling, leading to diffuse tissue damage, inflammatory spillover, and hampered axon regeneration. Corralling begins early and requires Plexin-B2 in both microglia and macrophages. Mechanistically, Plexin-B2 promotes microglia motility, steers IAM away from colliding cells, and facilitates matrix compaction. Our data thus establish Plexin-B2 as an important link that integrates biochemical cues and physical interactions of IAM with the injury microenvironment during wound healing.

2019-12-23 | GSE113566 | GEO

Plexin-B2-bound proteins purified by immunoprecipitation using anti-Plexin-B2 antibody

Project description:To identify Plexin-B2-associated proteins, articular chondrocytes were untreated or treated with Sema4D. Plexin-B2-bound proteins were purified by immunoprecipitation using an anti-Plexin-B2 antibody, followed by mass spectrometry.

2022-11-01 | PXD034551 | JPOST Repository

Plexin-B2 reduces glioma cell cohesion and regulates glioma-vascular interactions

Project description:Plexin-B2 reduces glioma cell cohesion and regulates glioma-vascular interactions

| PRJNA522815 | ENA

analysis of the immune and astrocytic cell fraction 12h after cortical injury in Sema4B knockout mice

Project description:After central nervous system injury, a rapid neuroinflammatory response is induced. This response can be both beneficial and detrimental to neuronal survival in the first few days and increase the risk for neurodegeneration if it persists. Semaphorin4B (Sema4B), a transmembrane protein primarily expressed by cortical astrocytes, has been shown to play a role in neuronal cell death following injury. Our study shows that neuroinflammation is attenuated in Sema4B knockout mice and microglia/macrophage activation is reduced after cortical stab wound injury. In vitro, recombinant Sema4B enhances the activation of microglia following injury, suggesting astrocytic Sema4B functions as a ligand. Moreover, injury-induced activation of microglia is attenuated in the presence of Sema4B knockout astrocytes compared to heterozygous astrocytes. In vitro, experiments indicate Plexin-B2 is the Sema4B receptor on microglia. Consistent with this, microglia-specific Plexin-B2 knockout mice, similar to Sema4B knockout mice, also show a reduction in microglial activation after cortical injury. Finally, in Sema4B/Plexin-B2 double heterozygous mice, microglial activation is also reduced after injury, thus supporting the idea that both Sema4B and Plexin-B2 are part of the same signaling pathway. Taken together, we propose a model in which following injury, astrocytic Sema4B enhances the pro-inflammatory response of microglia/macrophages via Plexin-B2, leading to increased neuroinflammation.

2024-02-28 | GSE230069 | GEO

Plexin B2 and Semaphorin 4C guide T-cell recruitment and function in the germinal center

Project description:Follicular T-helper (TFH) cells are essential for germinal center (GC) responses. TFH localization in GCs is controlled by chemo-guidance cues and antigen-specific adhesion. Here we define an antigen-independent, contact-dependent, adhesive guidance system for TFH cells. Unusual for amoeboid cell migration, the system is composed of transmembrane plexin B2 (PlxnB2) molecule that is highly expressed by GC B cells and its transmembrane binding partner semaphorin 4C (Sema4C) that is upregulated on TFH cells. Instead of effectuating repulsion as a ligand, Sema4C serves as the receptor to sense PlxnB2 and bias TFH migration inward at the GC edge to penetrate the GC territory. The absence of PlxnB2 from the GC or Sema4C from TFH cells causes TFH accumulation along the GC border, impairs TFH -B cell interactions and is associated with defective plasma cell production and affinity maturation. Therefore, Sema4C and PlxnB2 regulate GC TFH recruitment and function and optimal antibody responses.

2017-06-12 | GSE96819 | GEO

Microglia and macrophages promote corralling, wound compaction and recovery in spinal cord injury via Plexin-B2

Project description:Microglia and macrophages promote corralling, wound compaction and recovery in spinal cord injury via Plexin-B2

| PRJNA451532 | ENA

In vivo interaction screening reveals liver-derived constraints to metastasis [scRNA-Seq]

Project description:It is estimated that only 0.02% of disseminated tumor cells are able to seed overt metastases1. While this suggests the presence of environmental constraints to metastatic seeding, the landscape of host factors controlling this process remains largely unknown. Combining transposon technology2 and fluorescent niche labeling3, we developed an in vivo CRISPR activation screen to systematically investigate the interactions between hepatocytes and metastatic cells. Our approach enabled the identification of Plexin B2 as a critical host-derived regulator of liver colonization in colorectal, pancreatic cancer and melanoma syngeneic mouse models. We dissect a mechanism by which Plexin B2 interacts with class IV semaphorins on tumor cells, leading to Klf4 upregulation and thereby promoting the acquisition of epithelial traits. Our findings highlight the essential role of signals from the liver parenchyma for the seeding of disseminated tumor cells, prior to the establishment of a growth promoting niche. They further suggest that epithelialization is required for the adaptation of CRC metastases to their new tissue environment. Blocking the Plexin B2-semaphorin axis abolishes metastatic colonization of the liver and thus represents a new therapeutic strategy for the prevention of hepatic metastases. Finally, our screening approach, which evaluates host-derived extrinsic signals rather than tumor-intrinsic factors for their ability to promote metastatic seeding, is broadly applicable and lays a framework for the screening of environmental constraints to metastasis in other organs and cancer types.

2024-05-21 | GSE267981 | GEO

In vivo interaction screening reveals liver-derived constraints to metastasis [Single Cell Multiome ATAC + Gene Expression]

2024-05-21 | GSE267982 | GEO