Similar Datasets
Project description:STAT3 has been studied extensively in the context of self-renewal of naïve pluripotent mouse embryonic stem cells (mESCs). Although STAT3 is required to maintain ICM lineages when maternally eliminated, the role of STAT3 during gastrulation is unclear as the conventional knockout of Stat3 develops until E6.5. In this study, we observed that zygotic loss of Stat3 on CD1 genetic background leads to consistent developmental retardation from implantation to mid-gestation, beginning with a significant reduction in the number of epiblast cells by the time of implantation. Remarkably, mutants appear to scale normally and resemble non-affected embryos from the previous day at all postimplantation stages examined. Bulk RNA-seq analysis using isolated epiblast cells revealeed that E6.5 null epiblasts were intermediate between WT E5.5 and E6.5; E7.5 null epiblasts grouped more closely with WT E6.5 than E7.5 epiblasts. Gene ontology analysis revealed lipid metabolism was compromised in Stat3 null embryos as early as E6.5. Interestingly, Socs3, downstream target of STAT3, was not induced in WT rpiblast cells until E7.5. We found Y705 phospholylated STAT3 was not exist postimplantation epiblast, but S727 phoshorylated STAT3 was abundant over the time, suggesting postimplantation specific roles of S727 phosphorylated STAT3 in growth and differentiation. Our study revealed that while Stat3 null epiblast cells progress along a near normal differentiation trajectory, Stat3 deletion compromises lipid metabolism as early as E6.5.
2025-04-07 | GSE259342 | GEO
Project description:STAT3 has been studied extensively in the context of self-renewal of naïve pluripotent mouse embryonic stem cells (mESCs). Although STAT3 is required to maintain ICM lineages when maternally eliminated, the role of STAT3 during gastrulation is unclear as the conventional knockout of Stat3 develops until E6.5. In this study, we observed that zygotic loss of Stat3 on CD1 genetic background leads to consistent developmental retardation from implantation to mid-gestation, beginning with a significant reduction in the number of epiblast cells by the time of implantation. Remarkably, mutants appear to scale normally and resemble non-affected embryos from the previous day at all postimplantation stages examined. Bulk RNA-seq analysis using isolated epiblast cells revealeed that E6.5 null epiblasts were intermediate between WT E5.5 and E6.5; E7.5 null epiblasts grouped more closely with WT E6.5 than E7.5 epiblasts. Gene ontology analysis revealed lipid metabolism was compromised in Stat3 null embryos as early as E6.5. Interestingly, Socs3, downstream target of STAT3, was not induced in WT rpiblast cells until E7.5. We found Y705 phospholylated STAT3 was not exist postimplantation epiblast, but S727 phoshorylated STAT3 was abundant over the time, suggesting postimplantation specific roles of S727 phosphorylated STAT3 in growth and differentiation. Our study revealed that while Stat3 null epiblast cells progress along a near normal differentiation trajectory, Stat3 deletion compromises lipid metabolism as early as E6.5.
2025-04-07 | GSE254697 | GEO
Project description:STAT3 signalling drives tissue expansion during postimplantation mouse development
| PRJNA1082300 | ENA
Project description:STAT3 signalling drives tissue expansion during postimplantation mouse development [scRNA-seq]
| PRJNA1081299 | ENA
Project description:STAT3 signalling drives tissue expansion during postimplantation mouse development [RNA-seq]
| PRJNA1071539 | ENA
Project description:CDC45 is required for the initiation of DNA replication in Saccharomyces cerevisiae and functions as a DNA polymerase alpha loading factor in Xenopus, but its role in mammalian DNA replication is unknown. To investigate the genetic and physiological functions of CDC45, we used a gene targeting strategy to generate mice lacking a functional CDC45 gene. Homozygous mutant mice lacking a functional CDC45 gene underwent uterine implantation and induced uterine decidualization but did not develop substantially thereafter. Detailed analysis of CDC45 null embryos cultured in vitro revealed impaired proliferation of the inner cell mass. These findings make CDC45 the only putative replication factor experimentally proven to be essential for mammalian development. The CDC45 gene localizes to human chromosome 22q11.2 in the DiGeorge syndrome critical region (DGCR). Almost 90% of individuals with congenital cardiac and craniofacial defects have a monoallelic deletion in the DGCR that includes CDC45. We report here that heterozygous mutant mice develop into adulthood without any apparent abnormalities, so that it is unlikely that hemizygosity of CDC45 alone is responsible for the cardiac and craniofacial defects in the congenital syndromes.
| S-EPMC87121 | biostudies-literature
Project description:During tissue morphogenesis and differentiation, cells must self-renew while contemporaneously generating daughters that contribute to the growing tissue. How tissues achieve this precise balance between proliferation and differentiation is, in most instances, poorly understood. This is in part due to the difficulties in dissociating the mechanisms that underlie tissue patterning from those that regulate proliferation. In the migrating posterior lateral line primordium (PLLP), proliferation is predominantly localised to the leading zone. As cells emerge from this zone, they periodically organise into rosettes that subsequently dissociate from the primordium and differentiate as neuromasts. Despite this reiterative loss of cells, the primordium maintains its size through regenerative cell proliferation until it reaches the tail. In this study, we identify a null mutation in the Wnt-pathway transcription factor Lef1 and show that its activity is required to maintain proliferation in the progenitor pool of cells that sustains the PLLP as it undergoes migration, morphogenesis and differentiation. In absence of Lef1, the leading zone becomes depleted of cells during its migration leading to the collapse of the primordium into a couple of terminal neuromasts. We show that this behaviour resembles the process by which the PLLP normally ends its migration, suggesting that suppression of Wnt signalling is required for termination of neuromast production in the tail. Our data support a model in which Lef1 sustains proliferation of leading zone progenitors, maintaining the primordium size and defining neuromast deposition rate.
| S-EPMC3160090 | biostudies-literature
Project description:BackgroundPatients with metastatic bladder cancer have very poor prognosis and predictive biomarkers are urgently needed for early clinical detection and intervention. In this study, we evaluate the effect and mechanism of Suprabasin (SBSN) on bladder cancer metastasis.MethodsA tissue array was used to detect SBSN expression by immunohistochemistry. A tumour-bearing mouse model was used for metastasis evaluation in vivo. Transwell and wound-healing assays were used for in vitro evaluation of migration and invasion. Comprehensive molecular screening was achieved by western blotting, immunofluorescence, luciferase reporter assay, and ELISA.ResultsSBSN was found markedly overexpressed in bladder cancer, and indicated poor prognosis of patients. SBSN promoted invasion and metastasis of bladder cancer cells both in vivo and in vitro. The secreted SBSN exhibited identical biological function and regulation in bladder cancer metastasis, and the interaction of secreted SBSN and EGFR could play an essential role in activating the signalling in which SBSN enhanced the phosphorylation of EGFR and SRC kinase, followed with phosphorylation and nuclear location of STAT3.ConclusionsOur findings highlight that SBSN, and secreted SBSN, promote bladder cancer metastasis through activation of EGFR/SRC/STAT3 pathway and identify SBSN as a potential diagnostic and therapeutic target for bladder cancer.
| S-EPMC9296541 | biostudies-literature
Project description:White adipose tissue displays high plasticity. We developed a system for the inducible, permanent labeling of mature adipocytes that we called the AdipoChaser mouse. We monitored adipogenesis during development, high-fat diet (HFD) feeding and cold exposure. During cold-induced 'browning' of subcutaneous fat, most 'beige' adipocytes stem from de novo-differentiated adipocytes. During HFD feeding, epididymal fat initiates adipogenesis after 4 weeks, whereas subcutaneous fat undergoes hypertrophy for a period of up to 12 weeks. Gonadal fat develops postnatally, whereas subcutaneous fat develops between embryonic days 14 and 18. Our results highlight the extensive differences in adipogenic potential in various fat depots.
| S-EPMC4075943 | biostudies-literature
Project description:The hnRNP C1 and C2 proteins are among the most abundant proteins in the nucleus, and as ubiquitous components of RNP complexes, they have been implicated in many aspects of mRNA biogenesis. In this report, we have characterized a null mutation induced in embryonic stem cells by insertion of the U3His gene trap retrovirus into the first intron of the hnRNP C1/C2 gene. cDNAs encoding murine hnRNP C1 and C2 were characterized, and the predicted protein sequences were found to be highly conserved among vertebrates. A human consensus sequence, generated from over 400 expressed sequence tags, suggests two revisions to the previously published human sequence. In addition, alternatively spliced transcripts, expressed only by the murine gene, encode four novel proteins: variants of C1 and C2 with either seven additional amino acids or one fewer amino acid in a region between the oligomerization and C-terminal acidic domains. The disrupted gene was transmitted into the germ line and is tightly linked to a recessive, embryonic lethal phenotype. Homozygous mutant embryos fail to develop beyond the egg cylinder stage and are resorbed by 10.5 days of gestation, a phenotype consistent with a fundamental role in cellular metabolism. However, hnRNP C1 and C2 are not required for cell viability. Embryonic stem cell lines established from homozygous mutant blastocysts did not express detectable levels of either protein yet were able to grow and differentiate in vitro, albeit more slowly than wild-type cells. These results indicate that the C1 and C2 hnRNPs are not required for any essential step in mRNA biogenesis; however, the proteins may influence the rate and/or fidelity of one or more steps.
| S-EPMC85779 | biostudies-literature