Expression profile of Sall4-null ES cells and Sall4 heterozygous ES cells
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE14219 | GEO | 2009/04/01
SECONDARY ACCESSION(S): PRJNA111349
REPOSITORIES: GEO
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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
2009-04-01 | E-GEOD-14219 | biostudies-arrayexpress
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.
2016-08-02 | PXD003614 | Pride
Project description:This SuperSeries is composed of the following subset Series: GSE21054: Differential roles of Sall4 isoforms in ES cell pluripotency: expression GSE21055: Differential Role of Sall4 isoforms in ES cell pluripotency: ChIP-chip Refer to individual Series
2010-09-13 | E-GEOD-21056 | biostudies-arrayexpress
Project description:Sall4 is a stem cell factor which is important for embryogenesis. We have genetically modified Sall4 in mouse embryonic stem cells to access the preference of Sall4 binding site. There are three different genetic modifications for the ES cells in the form of Sall4 Knockout (KO), Sall4 Zinc Finger Cluster 4 Mutation (ZFC4mut) and Sall4 Zinc Finger Cluster 1-2 Deletion (ZFC1-2Δ) respectively that we have considered for our study.
2021-01-05 | E-MTAB-9197 | biostudies-arrayexpress
Project description:Murine embryonic stem cells (ESCs) are defined by continuous self-renewal and pluripotency. A diverse repertoire of protein isoforms arising from alternative splicing are expressed in ES cells without defined biological roles. Sall4, a transcription factor essential for pluripotency, exists as two isoforms (Sall4a and Sall4b). By genome-wide location analysis, we have determined that Sall4b, and not Sall4a, binds preferentially to highly expressed loci in ES cells. Sall4a and Sall4b binding sites are distinguished by both epigenetic marks at target loci and their clustering with binding sites of other pluripotency factors. When ESCs expressing a single isoform of Sall4 are generated, Sall4b alone could maintain the pluripotent state, although it could not completely suppress all differentiation markers. Sall4a and Sall4b collaborate in maintenance of the pluripotent state, but play distinct roles. Our work is novel in establishing such isoform-specific differences in ES cells.
2010-09-13 | GSE21054 | GEO
Project description:Embryonic stem cells have potential utility in regenerative medicine due to their pluripotent characteristics. Sall4, a zinc-finger transcription factor, is expressed very early in embryonic development with Oct4 and Nanog, two well characterized pluripotency regulators. Sall4 plays an important role in governing the fate of stem cells through transcriptional regulation of both Oct4 and Nanog. Using chromatin immunoprecipitation coupled to microarray hybridization (ChIP on Chip), we have mapped global gene targets of Sall4 unveiling possible regulation of broad ES cell functions. Approximately 5,000 genes were identified that were bound by the Sall4 protein and many of these have major functions in developmental and regulatory pathways. Sall4 bound more than six times as many annotated genes within promoter regions as Oct4 and twice as many as Nanog. Immunoprecipitation revealed a heterotrimeric protein complex between Sall4, Oct4, and Nanog, consistent with binding site co-occupancies. Further, Sall4 bound many genes that are regulated in part by the chromatin-based epigenetic events mediated by polycomb-repressive complexes and bivalent domains. This suggests that Sall4 plays a central and diverse role in regulating stem cell pluripotency during early embryonic development that involves integration of transcriptional and epigenetic control processes. Keywords: ChIP-chip We used ChIP-chip to map global promoter bound by Sall4, a zinc finger transcription factor. Growing evidence has suggested that Sall4 plays a vital role in ES cell pluripotency maintenance. Evidence for this includes its recent use as a marker for somatic cell reprogramming, in a genetic signature for ES cells, and evidence that Sall4 enhances reprogramming. These recent findings and two previously described interactions with Oct4 and Nanog strongly support the role of Sall4 in ES cells. This hypothesis was furthered here as we show that Sall4 plays important roles through transcriptional regulation of vital ES cell genes.
2008-09-01 | E-GEOD-11305 | biostudies-arrayexpress
Project description:Murine embryonic stem cells (ESCs) are defined by continuous self-renewal and pluripotency. A diverse repertoire of protein isoforms arising from alternative splicing are expressed in ES cells without defined biological roles. Sall4, a transcription factor essential for pluripotency, exists as two isoforms (Sall4a and Sall4b). By genome-wide location analysis, we have determined that Sall4b, and not Sall4a, binds preferentially to highly expressed loci in ES cells. Sall4a and Sall4b binding sites are distinguished by both epigenetic marks at target loci and their clustering with binding sites of other pluripotency factors. When ESCs expressing a single isoform of Sall4 are generated, Sall4b alone could maintain the pluripotent state, although it could not completely suppress all differentiation markers. Sall4a and Sall4b collaborate in maintenance of the pluripotent state, but play distinct roles. Our work is novel in establishing such isoform-specific differences in ES cells.
2010-09-13 | GSE21055 | GEO
Project description:POU transcription factor Pou5f1 (Oct3/4) is required to maintain ES cells in an undifferentiated state. Here we show that global expression profiling of Oct3/4-manipulated ES cells delineates the downstream target genes of Oct3/4. Combined with data from genome-wide chromatin-immunoprecipitation assays, this analysis identifies not only primary downstream targets of Oct3/4, but also secondary or tertiary targets. Furthermore, the analysis also reveals that downstream target genes are regulated either positively or negatively by Oct3/4. Identification of a group of genes that show both activation and repression depending on Oct3/4 expression levels provides a possible mechanism for the requirement of appropriate Oct3/4 expression to maintain undifferentiated ES cells. As a proof-of-principle study, one of the downstream genes, Tcl1, has been analyzed in detail. We show that Oct3/4 binds to the promoter region of Tcl1 and activates its transcription. We also show that Tcl1 is involved in the regulation of proliferation, but not differentiation, in ES cells. These findings suggest that the global expression profiling of gene-manipulated ES cells can help to delineate the structure and dynamics of gene regulatory networks. Keywords: development or differentiation design,time series design ZHBTc4, ZHTc6, and EB5 ES cells were cultured without feeder cells in LIF-supplemented medium as described . For differentiation, ZHTc6 cells were cultured in the absence of Tet, which induced the overexpression of Oct3/4. ZHBTc4 cells were cultured in the presence of Tet, repressing Oct3/4 expression. Trophoblast stem (TS) cells and another ES cell line (R1) were cultured as previously described . Three independent samples were prepared for each time point. Microarray experiments were carried out as described using the NIA Mouse 22K Microarray v1.0.
2010-06-30 | E-GEOD-5936 | biostudies-arrayexpress
Project description:Stem cells self-renew or differentiate under the governance of a stem cell-specific transcriptional program with each transcription factor orchestrating the activities of a particular set of genes. Here we demonstrate that a single transcription factor is able to regulate distinct core circuitries in two different blastocyst-derived stem cell lines, embryonic stem (ES) and extra-embryonic endoderm (XEN) cells. The transcription factor, Sall4, is required for early embryonic development and for ES cell pluripotency. Sall4 is also expressed in XEN cells and depletion of Sall4 disrupts self-renewal and induces differentiation. Genome-wide analysis reveals Sall4 is regulating different gene sets in ES and XEN cells, and depletion of Sall4 targets in the respective cell types induces differentiation. With Oct4, Sox2 and Nanog, Sall4 forms a crucial interconnected auto-regulatory network in ES cells. In XEN cells, Sall4 regulates key XEN lineageassociated genes, Gata4, Gata6, Sox7 and Sox17. Our findings demonstrate how Sall4 functions as an essential stemness factor for two different stem cell lines. Keywords: ES/XEN comparison, ES Sall4 KD/control KD comparison, and XEN Sall4 KD/control KD comparison
2008-08-19 | GSE12482 | GEO
Project description:Embryonic stem cells have potential utility in regenerative medicine due to their pluripotent characteristics. Sall4, a zinc-finger transcription factor, is expressed very early in embryonic development with Oct4 and Nanog, two well characterized pluripotency regulators. Sall4 plays an important role in governing the fate of stem cells through transcriptional regulation of both Oct4 and Nanog. Using chromatin immunoprecipitation coupled to microarray hybridization (ChIP on Chip), we have mapped global gene targets of Sall4 unveiling possible regulation of broad ES cell functions. Approximately 5,000 genes were identified that were bound by the Sall4 protein and many of these have major functions in developmental and regulatory pathways. Sall4 bound more than six times as many annotated genes within promoter regions as Oct4 and twice as many as Nanog. Immunoprecipitation revealed a heterotrimeric protein complex between Sall4, Oct4, and Nanog, consistent with binding site co-occupancies. Further, Sall4 bound many genes that are regulated in part by the chromatin-based epigenetic events mediated by polycomb-repressive complexes and bivalent domains. This suggests that Sall4 plays a central and diverse role in regulating stem cell pluripotency during early embryonic development that involves integration of transcriptional and epigenetic control processes. Keywords: ChIP-chip
2008-09-01 | GSE11305 | GEO