Project description:Sall4 is a mouse homolog of a causative gene of the autosomal dominant disorder known as Okihiro syndrome. We previously showed that Sall4 absence leads to lethality during peri-implantation and that Sall4-null embryonic stem (ES) cells proliferate poorly with intact pluripotency when cultured on feeder cells. However, a subsequent report indicated that shRNA-mediated Sall4 inhibition in ES cells led to a severe reduction in Oct3/4 and a secondary increase in Cdx2, which resulted in complete differentiation into the trophectoderm when cultured in the feeder-free condition. So we profiled gene expression changes when Sall4 is deleted in ES cells in the presence or absence of feeder cells. key word: embryonic stem (ES) cell, Sall4, feeder
Project description:Sall4 is a transcription factor essential for early mammalian development. Though it is reported to play an important role in embryonic stem (ES) cell self-renewal, whether it is an essential pluripotency factor has been disputed. Though Sall4 is known to associate with the Nucleosome Remodeling and Deacetylase (NuRD) complex, the nature of this interaction is unclear as NuRD and Sall4 serve opposing functions in ES cells. Here we use defined culture conditions and single-cell gene expression analyses to show that Sall4 prevents activation of the neural gene expression programme in ES cells but is dispensable for maintaining the pluripotency gene regulatory network. We further show using genome-wide analyses that while Sall4 interacts with NuRD, it neither recruits NuRD to chromatin nor influences transcription via NuRD. Rather we propose a model where, by titrating Sall4 protein, NuRD limits the differentiation-inhibiting activity of Sall4 in ES cells to enable lineage commitment.
Project description:Sall4 is a mouse homolog of a causative gene of the autosomal dominant disorder known as Okihiro syndrome. We previously showed that Sall4 absence leads to lethality during peri-implantation and that Sall4-null embryonic stem (ES) cells proliferate poorly with intact pluripotency when cultured on feeder cells. However, a subsequent report indicated that shRNA-mediated Sall4 inhibition in ES cells led to a severe reduction in Oct3/4 and a secondary increase in Cdx2, which resulted in complete differentiation into the trophectoderm when cultured in the feeder-free condition. So we profiled gene expression changes when Sall4 is deleted in ES cells in the presence or absence of feeder cells. key word: embryonic stem (ES) cell, Sall4, feeder ES cells were cultured with or without mouse embryonic fibroblast (MEF) feeder cells in LIF-supplemented medium as described. To maintain the expression of Oct3/4, all ES cells were cultured in the presence of Blasticidin. Four samples were analyzed. GSM356329, GSM356330 : cultured in the absence of feeders GSM356331, GSM356332 : cultured on the feeders
Project description:To describe the protein profile in hippocampus, colon and ileum tissue’ changing after the old faeces transplants, we adopted a quantitative label free proteomics approach.
Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.
Project description:We created mice, which are deficient for Myc specifically in cardiac myocytes by crossing crossed Myc-floxed mice (Mycfl/fl) and MLC-2VCre/+ mice. Serial analysis of earlier stages of gestation revealed that Myc-deficient mice died prematurely at E13.5-14.5. Morphological analyses of E13.5 Myc-null embryos showed normal ventricular size and structure; however, decreased cardiac myocyte proliferation and increased apoptosis was observed. BrdU incorporation rates were also decreased significantly in Myc-null myocardium. Myc-null mice displayed a 3.67-fold increase in apoptotic cardiomyocytes by TUNEL assay. We examined global gene expression using oligonucleotide microarrays. Numerous genes involved in mitochondrial death pathways were dysregulated including Bnip3L and Birc2. Keywords: wildtype vs Myc-null
Project description:PURPOSE: To provide a detailed gene expression profile of the normal postnatal mouse cornea. METHODS: Serial analysis of gene expression (SAGE) was performed on postnatal day (PN)9 and adult mouse (6 week) total corneas. The expression of selected genes was analyzed by in situ hybridization. RESULTS: A total of 64,272 PN9 and 62,206 adult tags were sequenced. Mouse corneal transcriptomes are composed of at least 19,544 and 18,509 unique mRNAs, respectively. One third of the unique tags were expressed at both stages, whereas a third was identified exclusively in PN9 or adult corneas. Three hundred thirty-four PN9 and 339 adult tags were enriched more than fivefold over other published nonocular libraries. Abundant transcripts were associated with metabolic functions, redox activities, and barrier integrity. Three members of the Ly-6/uPAR family whose functions are unknown in the cornea constitute more than 1% of the total mRNA. Aquaporin 5, epithelial membrane protein and glutathione-S-transferase (GST) omega-1, and GST alpha-4 mRNAs were preferentially expressed in distinct corneal epithelial layers, providing new markers for stratification. More than 200 tags were differentially expressed, of which 25 mediate transcription. CONCLUSIONS: In addition to providing a detailed profile of expressed genes in the PN9 and mature mouse cornea, the present SAGE data demonstrate dynamic changes in gene expression after eye opening and provide new probes for exploring corneal epithelial cell stratification, development, and function and for exploring the intricate relationship between programmed and environmentally induced gene expression in the cornea. Keywords: other