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Dmrt1 maintains testicular immune homeostasis by activating Spry1 and inhibiting NF-κB signaling pathway [Spry1 KD RNA-Seq]

ABSTRACT: To explore the function of Spry1 in testis, we constructed a mouse model with testicular specific KD of Spry1 through seminiferous tubule transplantation

ORGANISM(S): Mus musculus

PROVIDER: GSE212667 | GEO | 2023/09/01

REPOSITORIES: GEO

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Dmrt1 maintains testicular immune homeostasis by activating Spry1 and inhibiting NF-κB signaling pathway [Dmrt1 RNA-Seq]

Project description:To explore the potential function of Dmrt1 in spermatogenesis, we constructed a Dmrt1-deficiency mouse model by knockdown Dmrt1 in testicular seminiferous tubule specifically

2023-09-01 | GSE212664 | GEO

Dmrt1 maintains testicular immune homeostasis by activating Spry1 and inhibiting NF-κB signaling pathway

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-09-01 | GSE212668 | GEO

Dmrt1 maintains testicular immune homeostasis by activating Spry1 and inhibiting NF-κB signaling pathway [ChIP-Seq]

Project description:In order to explore the mechanisms of Dmrt1 in regulating testicular immune homeostasis, we performed ChIP-seq analysis on primary SCs infected with a lentiviral vector expressing FLAG-tagged Dmrt1

2023-09-01 | GSE212665 | GEO

Loss of Spry1 reduces growth of BRAFV600E-mutant cutaneous melanoma and improves response to targeted therapy

Project description:Mitogen-activated protein kinase (MAPK) pathway activation is a central step in BRAFV600E-mutant cutaneous melanoma (CM) pathogenesis. In the last years, Spry1 has been frequently described as an upstream regulator of MAPK signaling pathway. However, its specific role in BRAFV600E-mutant CM is still poorly defined. Here, we report that Spry1 knockdown (Spry1KO) in three BRAFV600E-mutant CM cell lines markedly induced cell cycle arrest and apoptosis, repressed cell proliferation in vitro, and impaired tumor growth in vivo. Furthermore, our findings indicated that Spry1KO reduced the expression of several EMT-markers, such as MMP-2 both in vitro and in vivo. These effects were associated with a sustained and deleterious phosphorylation of ERK1/2. In addition, p38 activation along with an increase in basal ROS levels were found in Spry1KO clones compared to parental CM cell lines, suggesting that BRAFV600E-mutant CM may restrain the activity of Spry1 to avoid oncogenic stress and to enable tumor growth. Consistent with this hypothesis, treatment with the BRAF inhibitor (BRAFi) vemurafenib down-regulated Spry1 levels in parental CM cell lines, indicating that Spry1 expression is sustained by MAPK/ERK signaling pathway in a positive feedback loop that safeguards cells from the potentially toxic effects of ERK1/2 hyperactivation. Disruption of this feedback loop rendered Spry1KO cells more susceptible to apoptosis and markedly improved response to BRAFi both in vitro and in vivo, as a consequence of the detrimental effect of ERK1/2 hyperactivation observed upon Spry1 abrogation. Therefore, targeting Spry1 might offer a treatment strategy for BRAFV600E-mutant CM by inducing the toxic effects of ERK-mediated signaling.

2020-05-26 | E-MTAB-7886 | biostudies-arrayexpress

Role and function of SPRY1/2 in BCR-ABL1 driven pre-B cells

Project description:In order to investigate the function of SPRY1 and SPRY2 in ALL, we isolated bone marrow cells from Spry1 and 2 fl/fl mice and transformed them with BCR-ABL1. In a second transduction the BCR-ABL1 driven pre-B cells were transformed either with CRE-ERT2 or ERT2 (PMIP) and after 2 days of treatment with 4OH-Tamoxifen (0.5 micromolar) subjected to gene expression analysis.

2013-06-03 | GSE34834 | GEO

Role and function of SPRY1/2 in BCR-ABL1 driven pre-B cells

2013-06-03 | E-GEOD-34834 | biostudies-arrayexpress

Potency of Testicular Somatic Environment to Support Spermatogenesis in XX/Sry Transgenic Male Mice

Project description:Sry is sufficient to induce testis formation and subsequent male development of internal and external genitalia in chromosomally female mice and humans. In XX sex-reversed males such as XX/Sry-transgenic (XX/Sry) mice, however, testicular germ cells always disappear soon after birth due to germ cell autonomous defects. Therefore, it remains unclear whether or not Sry alone is sufficient to induce a fully functional testicular soma capable of supporting complete spermatogenesis in the XX body. Here we demonstrated that the testicular somatic environment of XX/Sry males is defective in the later phases of spermatogenesis. Spermatogonial transplantation analyses using XX/Sry male mice revealed that donor XY spermatogonia are capable of proliferating, entering meiosis and differentiating into the round spermatid stage. XY donor-derived round spermatids, however, were frequently detached from the XX/Sry seminiferous epithelia and underwent cell death, thereby preventing further progress beyond the elongated spermatid stage. In contrast, immature XY seminiferous tubule segments transplanted under XX/Sry testis capsules clearly displayed proper differentiation into elongated spermatids in the transplanted XY donor tubules. Microarray analysis of seminiferous tubules isolated from XX/Sry testes confirmed missing expression of several Y-linked genes and alterations in the expression profile of genes associated with spermatogenesis. Therefore, our findings indicate dysfunction of the somatic tubule components, probably Sertoli cells, of XX/Sry testes, supporting our hypothesis that Sry alone is insufficient to induce a fully functional Sertoli cell in XX mice. Keywords: comparative genomic hybridization

2007-07-15 | GSE5319 | GEO

Tumor fibroblast-derived FGF2 regulates SPRY1 expression in esophageal tumor-infiltrating T cells and plays a role in T cell exhaustion

Project description:Using single-cell RNA sequencing, we found that exhausted T cells in esophageal cancer were more heterogeneous than previously clarified. We discovered that SPRY1 was notably enriched in two subsets of exhausted CD8+ T cells. When overexpressed, SPRY1 impaired T cell activation by interacting with CBL, which is a negative regulator of ZAP-70 tyrosine phosphorylation.

2023-08-21 | GSE156585 | GEO

Next-generation sequencing to characterize the molecular basis for the differentiation of ES cells into testicular somatic cell-like cells and germ cell-like cells

Project description:Taking advantage of the tesco-cfp transgenic mouse line in which CFP is exclusively expressed in Sertoli cells under the control of a testis-specific enhancer (tesco), we established an embryonic stem cell from the mouse line (i.e. tcESC). We also created tcESC constitutively expressing mouse Sf1 transgene (tc;Sf1ESC). When we induced the differentiation of the two ESC lines into testicular somatic cell-like cells (TesLCs), tc;Sf1ESCs efficiently developed seminiferous tubule-like structures with the appearance of CFP-positive Setoli cell-like cells (SCLCs) in the tubules. On the other hand, epiblast-like cells (EpiLCs) were generated from ESCs having a germ cell-specific Prdm1-gfp transgene. Co-culture of tc;Sf1TesLCs with Prdm1-gfp EpiLCs resulted in self-organised aggregates, or testicular organoids. In the organoid, the EpiLCs differentiated into GFP-positive PGCLCs or gonocyte-like cells that were enclosed within a seminiferous tubule-like structure composed of CFP-positive SCLCs.

2021-06-18 | GSE149932 | GEO

RNA-seq analysis comparing Spry1flox/flox mice back epidermis to the back epidermis derived from Spry1 epidermis specific knockout mice

Project description:We found that Spry1 epidermis specific knockout give rise to back epidermis hyperpigmentaiton highly mimicks tanning response in mouse

2024-02-21 | GSE232912 | GEO

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