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SIRT1 deficiency enhances RA induced mESC differentiation

ABSTRACT: Retinoid homeostasis is critical for normal embryonic development, and both the deficiency and excess of these compounds are associated with congenital malformations. Here we found that SIRT1, the most conserved mammalian NAD+-dependent deacetylase, contributes to the maintenance of homeostatic retinoic acid (RA) signaling and modulates mouse embryonic stem cell (mESC) differentiation. Our data show that SIRT1 deficiency enhances RA signaling, thereby accelerating mES cell differentiation in response to RA. Our findings highlight the importance of SIRT1 in transcriptional regulation of ESC pluripotency and embryogenesis.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE59140 | GEO | 2014/08/21

SECONDARY ACCESSION(S): PRJNA254494

REPOSITORIES: GEO

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SIRT1 deficiency enhances RA induced mESC differentiation

Project description:Retinoid homeostasis is critical for normal embryonic development, and both the deficiency and excess of these compounds are associated with congenital malformations. Here we found that SIRT1, the most conserved mammalian NAD+-dependent deacetylase, contributes to the maintenance of homeostatic retinoic acid (RA) signaling and modulates mouse embryonic stem cell (mESC) differentiation. Our data show that SIRT1 deficiency enhances RA signaling, thereby accelerating mES cell differentiation in response to RA. Our findings highlight the importance of SIRT1 in transcriptional regulation of ESC pluripotency and embryogenesis. Three pairs of sh-Control and sh-SIRT1 E14 mESC cells (with dulpicate for each sample) were treated with vehicle ethanol or with 20 nM of RA for 2 days. Total RNA was isolated using a Qiagen RNA easy mini kit with on-column DNAseI treatment. RNA quality was validated with the Agilent 2100 Bioanalyzer in the microarray facility. Three-pairs of ethanol treated samples, and 4 RA treated sh-Control, and 6 RA treated sh-SIRT1 samples were analyzed by Agilent Whole Mouse Genome 4x44 formate oligo arrays (014868) (Agilent Technologies) following the Agilent 1-color microarray-based gene expression analysis protocol.

2014-08-21 | E-GEOD-59140 | biostudies-arrayexpress

LOXL2 dependent genes in RA induced mES differentiation

Project description:Our results indicate that oxidation of TAF10 by LOXL2 induces its release from its promoters, leading to a block in TFIID-dependent gene transcription. Since TFIID complex is crucial for the expression of Nanog, Klf4, Sox2 and Oct4 and for maintaining the pluripotent state of embryonic stem cells, TAF10 oxidation by LOXL2 leads to inactivation of the pluripotency genes and a loss of pluripotent capacity in embryonic stem cells. Moreover, in vivo results demonstrate an essential role of LOXL2 in neural differentiation during zebrafish development: in the absence of LOXL2 the neural progenitor gene Sox2 is aberrantly overexpressed and neural differentiation is impaired. 12 samples were analyzed: mES transduced with control shRNA (n=3); mES transduced with LOXL2 shRNA (n=3), ES transduced with control shRNA and treated with RA (n=3); ES transduced with LOXL2 shRNA and treated with RA (n=3)

2015-12-21 | E-GEOD-65675 | biostudies-arrayexpress

Accelerating Medicines Partnership-Rheumatoid Arthritis (AMP-RA)

Project description:Accelerating Medicines Partnership-Rheumatoid Arthritis (AMP-RA)

| PRJNA407593 | ENA

A SIRT1-centered Circuitry Regulates Breast Cancer Stemness and Metastasis

Project description:Deficiency of deacetylase SIRT1 or its downstream target PRRX1 promotes breast cancer stemness and metastasis. To explore the mechnisms of SIRT1 and its downstream target PRRX1 in breast cancer, we analysed the gene expressions in breast cancer BT549 cells with SIRT1 knockout or PRRX1 knockout or not.

2018-03-28 | GSE112365 | GEO

Methylated CpG Island Recovery Assay (MIRA)-chip from Sirt1 wild-type (Sirt1+/+) and knock-out (Sirt1-/-) murine embryonic stem cells (ESCs)

Project description:Proper DNA-methylation is inevitable for normal development and this epigenetic program is dynamically reprogrammed especially around embryo implantation. Accordingly, embryonic stem cells (ESCs) derived from inner cell mass in pre-implantation embryo exhibit the lowest DNA methylation level compared with differentiated tissue cells to ensure their pluripotency and germ-line potency. Methylated CpG Island Recovery Assay (MIRA) coupled chip DNA methylome analysis demonstrated that Sirt1 deficiency increases the abnormal DNA methylation especially on the a subtype of imprinted and germ-line development genes.

2017-02-20 | GSE60636 | GEO

Mus musculus

Project description:SIRT1 deficiency enhances RA induced mESC differentiation

| PRJNA254494 | ENA

RA-induced prominence-specific response resulted in distinctive regulation of Wnt and osteogenesis [miRNA-seq]

Project description:Proper retinoic acid (RA) signaling is essential for normal craniofacial development. Both excessive RA and RA deficiency in early embryonic stage led to a variety of craniofacial malformations, e.g., cleft palate, which have been investigated extensively. Dysregulated Wnt and Shh signaling were shown to underlie the pathogenesis of RA-induced craniofacial defects. In our present study, we showed a spatiotemporal-specific effect of RA signaling in regulating early development of facial prominences. While inhibited the Wnt activities in E12.5/E13.5 mouse palatal shelves, early exposure of excessive RA induced Wnt signaling and Wnt-related gene expression in mouse embryonic Frontonasal/Maxillary processes. A conserved regulatory network of miR-484-Fzd5 was identified to play critical roles in RA regulated craniofacial development using RNA-seq.

2023-07-29 | GSE238063 | GEO

RA-induced prominence-specific response resulted in distinctive regulation of Wnt and osteogenesis [mRNA-seq]

2023-07-29 | GSE238062 | GEO

Rhodothermaceae bacterium RA strain:RA

Project description:Rhodothermaceae bacterium RA strain:RA Genome sequencing

| PRJNA308615 | ENA

Genomewide gene expression analysis of murine Sirt1 wild-type or knock-out embryonic stem cells (ESCs)

Project description:Stem-cells and transformed cancer cells specifically express a polycomb repressive complex subtype, PRC4 which characteristically contains Sirt1 (Sirtuin-1), a NAD+ dependent class III histone deacetylase (HDAC) and Eed2 isoform as specific members. Analyzing the transcriptiome and methylome analysis of Sirt1 deficient murine ESCs (Sirt1-/- ESC), we demonstrate that these cells repressed specifically on some genomic imprinted and germ-line related genes. We used microarrays to characterize the programm of gene expression affected by Sirt1 in murine ESCs and identified distinct classes of down-regulated genes upon Sirt1 deficiency

2017-02-20 | GSE60500 | GEO

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