FGFR3 is Expressed by Human Primordial Germ Cells and is Repressed after Meiotic Initiation to Form Primordial Oocytes
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PROVIDER: PRJNA796329 | ENA |
REPOSITORIES: ENA
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Project description:Human germ cell development is a highly regulated process beginning soon after embryo implantation with the specification of primordial germ cells (PGCs) and ending in adulthood with the differentiation of gametes. Here, we show that fibroblast growth factor receptor 3 (FGFR3) is expressed by human PGCs during the first and second trimester, becoming repressed as PGCs differentiate into primordial oocytes. Using fluorescence activated cell sorting (FACS) with antibodies that recognize FGFR3 followed by single cell RNA sequencing, we show that isolating FGFR3-positive cells enriches for human PGCs. Taken together, FGFR3 could be used in future studies as a strategy to identify maturing hPGCs.
2022-05-19 | GSE193474 | GEO
Project description:Serine/arginine-rich splicing factor 1 (SRSF1; previously SF2/ASF) is a pivotal posttranscriptional regulator of gene expression in various biological processes. However, the physiological roles and mechanism of SRSF1 in mouse early-stage oocytes remain elusive. Here we show that SRSF1 is essential for primordial follicle formation and number determination during meiotic prophase I. The conditional knockout of Srsf1 in mouse oocytes impairs primordial follicle formation and leads to primary ovarian insufficiency (POI). Oocyte-specific genes (e.g., LHX8, NOBOX, SOHLH1, SOHLH2, FIGLA, KIT, JAGGED1, and RAC1) that regulate primordial follicle formation are suppressed in newborn Stra8-GFPCre Srsf1Fl/Fl (cKO) mouse ovaries. However, meiotic defects are the leading cause of abnormal primordial follicle formation. In cKO mouse ovaries, immunofluorescence results suggest that the failure of synapsis and the inability to undergo recombination result in fewer homologous DNA crossovers (COs). Moreover, SRSF1 directly binds and regulates the expression of the POI-related genes Six6os1 and Msh5 via alternative splicing to implement the meiotic prophase I program. Altogether, our data reveal a critical role of the SRSF1-mediated posttranscriptional regulatory mechanism in the mouse oocyte meiotic prophase I program, which provides a framework to elucidate molecular mechanisms of the posttranscriptional network underlying primordial follicle formation.
2023-02-06 | GSE198205 | GEO
Project description:To better understand the molecular mechanisms underlying altered-FGFR3 oncogenic activity in bladder carcinomas, we made use of UMUC-14 cell lines, which endogenously expressed a mutated activated form of FGFR3 (FGFR3-S249C), the growth and transformation of these cell lines being dependent on activated-FGFR3 activity. We conducted a gene expression analysis using Affymetrix DNA arrays in this cell line treated or not with FGFR3 siRNAs.
2020-12-31 | GSE125547 | GEO
Project description:To better understand the molecular mechanisms underlying altered-FGFR3 oncogenic activity in bladder carcinomas, we made use of MGH-U3 cell lines, which were derived from a human bladder tumor and endogenously expressed a mutated activated form of FGFR3 (FGFR3-Y375C), the growth and transformation of these cell lines being dependent on activated-FGFR3 activity. We conducted a gene expression analysis using Affymetrix DNA arrays in this cell line treated or not with FGFR3 siRNAs.
2018-02-16 | GSE84731 | GEO
Project description:To better understand the molecular mechanisms underlying altered-FGFR3 oncogenic activity in bladder carcinomas, we made use of RT112 cell lines, which were derived from a human bladder tumor and endogenously expressed the FGFR3-TACC3 fusion protein, the growth and transformation of these cell lines being dependent on activated-FGFR3 activity. We conducted a gene expression analysis using Affymetrix DNA arrays in this cell line treated or not with FGFR3 siRNAs.
2018-02-16 | GSE84732 | GEO
Project description:We employed dermal fibroblasts isolated from Fgfr3G374Rneo+ mice, which do not express functional Fgfr3 (Fgfr3KO), from Fgfr3G374Rneo- mice with ligand-independent constitutive activation of Fgfr3 (Fgfr3Act) and from wildtype (WT) mice with normal expression of Fgfr3. Total RNA from these murine dermal fibroblasts (passage 4) were extracted and after quality control, were hybridized to the murine genome U74 gene chip. We have identified that Fgfr3 regulates important profibrotic pathways in fibroblasts. Selective upregulation of fibroblast growth factor receptor 3 (FGFR3) and its ligand FGF9 promote fibroblast activation and tissue fibrosis Transcriptome profiling, in silico analysis and functional experiments revealed that FGFR3 synergistically induces multiple profibrotic pathways including Endothelin-, Interleukin-4- and CTGF-signaling in a CREB-dependent manner. Inhibition of FGFR3 signaling by fibroblast-specific knockout of FGFR3 or FGF9 or pharmacological inhibition of FGFR3 inhibited fibroblast activation and attenuated experimental skin fibrosis. We have characterized FGFR3 as an upstream regulator of a network of profibrotic mediators and as a potential target for the treatment of fibrosis.
2020-10-01 | GSE148643 | GEO
Project description:Neurotrophins are growth factors that are known to have a role in promoting cell survival and differentiation. The focus of the current study is to examine the role of neurotrophins in regulating ovarian primordial follicle development. Ovaries from 4-day old rats were placed into organ culture and cultured for 10 days in the absence or presence of neurotrophin-3 (NT3), brain-derived neurotrophic factor (BDNF), or nerve growth factor (NGF). Treatment of ovaries with NT3 resulted in a significant (P<0.01) increase in primordial follicle development (i.e. primordial to primary follicle transition). Treatment with BDNF at high doses of 100â250 ng/ml also significantly (P<0.01) increased primordial follicle development, but NGF had no effect. Immunohistochemical studies determined that NT3 was present in granulosa cells, interstitial tissue, and in the oocytes of primordial and primary follicles. The NT3 receptor NTRK3 was present in oocytes at all stages of development. Analysis of ovaries that contain predominantly primordial follicles demonstrated the transcripts for NT3, NTRK3, NGF, and the BDNF/neurotrophin-4 (NT4) receptor NTRK2 are expressed, while BDNF, NT4, and the NGF receptor NTRK1 are not detectable. Inhibition of the NTRK3 receptor with the tyrophostin AG 879 resulted in oocyte death and a significant (P<0.01) reduction in follicle pool size. Inhibition of the NTRK receptors with K252a slowed primordial to primary follicle transition. A microarray analysis demonstrated that a small number of genes were differentially expressed after NT3 treatment. Observations indicate that the neurotrophin NT3, acting through the NTRK3 receptor in oocytes, promotes the primordial to primary follicle transition. Reproduction (2009) 138, pp. 697-707 We used microarrays to determine genes expressed differentially between control and NT3 (neurotrophin-3) treated P4 ovary. RNA samples from 3 control groups are compared to 3 NT3 treated ovary groups.
2010-02-21 | E-GEOD-20358 | biostudies-arrayexpress
Project description:In order to interrogate the transcriptional changes elicited by FGFR3-TACC3, we expressed the FGFR3-TACC3 fusion protein in human astrocytes and compared the global gene expression profiles of cells treated with a specific inhibitor of FGFR3-TK (PD173074) or vehicle. FGFR3-TACC3 expressing HA were also compared with HA that expressed the kinase-inactive FGFR3-TACC3 (FGFR3-TACC3-K508M) and HA transduced with the empty vector. Gene Ontology-guided enrichment map demonstrated that, besides the expected enrichment for mitotic activity, oxidative phosphorylation and mitochondrial biogenesis were the most significant biological functions enriched in HA expressing active FGFR3-TACC3.
2017-10-17 | E-MTAB-6037 | biostudies-arrayexpress
Project description:Long-term reproductive ability in mammalian females is sustained by the successive consumption of the finite pool of primordial follicles, the most primitive ovarian follicles that arise from cystic-oocytes during oogenesis. However, mechanisms underlying the formation of primordial follicles are largely unknown. Here we show that dynamic conversion of RNA-regulatory proteins precedes the formation of primordial follicles in mice. We find that, whereas stress granules dominate in cystic-oocytes, those are replaced by processing-bodies prior to the formation of primordial follicles that coincide with the expression of an evolutionally conserved RNA-binding protein, DDX6. Targeted deletion of Ddx6 disrupts processing-body assembly and perturbs cyst-breakdown. Furthermore, these events are orchestrated by an RNA-binding protein, ELAVL2. Our data suggest that cystic-oocytes switch post-transcriptional mechanism for upcoming formation of primordial follicles.
2018-09-30 | GSE113304 | GEO