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LSD1 Conditional Knockout Mice Have an Increased Bone Mass Due to Increased IFN-B Gene Expression

ABSTRACT: LSD1 Conditional Knockout Mice Have an Increased Bone Mass Due to Increased IFN-B Gene Expression

PROVIDER: PRJNA1029587 | ENA |

REPOSITORIES: ENA

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LSD1 Conditional Knockout Mice Have an Increased Bone Mass Due to Increased IFN-B Gene Expression

Project description:Osteoclasts are large multinucleated cells that degrade bone mineral and extracellular matrix. Investigating the mechanisms by which osteoclast differentiation is epigenetically regulated is a key to understanding the pathogenesis of skeletal related diseases such as periodontitis and osteoporosis. Lysine specific demethylase 1 (LSD1/KDM1A) is a member of the histone demethylase family that regulates gene expression via the removal of mono- and dimethyl groups from H3K4 and H3K9. Prior to our study, little was known about the effect of LSD1 on skeletal development and osteoclast differentiation. Here we show conditional deletion of LSD1 in the myeloid lineage or macrophage/osteoclast precursors results in a decrease in osteoclast differentiation and activity. Our bulk RNA-SEQ data suggests that osteoclast differentiation is inhibited in LSD1cKO mice due to an increase in expression of IFN-b target genes. Lastly, we demonstrate that LSD1 can form a complex with CoREST, HDAC1 and HDAC2 suggesting a mechanism by which the combination of methylation and acetylation of histone residues regulates osteoclast gene expression.

2024-10-11 | GSE245698 | GEO

LSD1 regulates the plasmablast transcriptome

Project description:To understand the role of LSD1 in B cell differentiation, mice with B cell conditional deletion of LSD1 were intravenously inoculated with LPS. After 3 days, B220+GL7-CD138- naïve B cells and CD138+ plasmablasts were FACS-sorted from the spleens and RNA-seq was performed to identify LSD1-target regulated genes.

2018-09-06 | GSE114775 | GEO

LSD1 regulates plasmablast chromatin accessibility

2018-09-06 | GSE114774 | GEO

LSD1 regulates splenic B cell chromatin accessibility

Project description:To understand the role of LSD1 in splenic B cell development, spleens from mice with B cell conditional deletion of LSD1 were harvested, B220+CD93–GL7–CD23–CD21hiCD1d+ marginal zone B cells and B220+CD93–GL7–CD23+CD21midCD1d– follicular B cells were FACS-sorted, and ATAC-seq was performed to identify LSD1-target regulated chromatin.

2019-08-06 | GSE132196 | GEO

LSD1 regulates the marginal zone B cell transcriptome

Project description:To understand the role of LSD1 in splenic B cell development, spleens from mice with B cell conditional deletion of LSD1 were harvested, B220+CD93–GL7–CD23–CD21hiCD1d+ marginal zone B cells and B220+CD93–GL7–CD23+CD21midCD1d– follicular B cells were FACS-sorted, and RNA-seq was performed to identify LSD1-target regulated genes.

2019-08-06 | GSE132197 | GEO

LSD1 regulates the plasmablast transcriptome

Project description:To understand the role of LSD1 in marginal zone B cell development, CD93+ transitional B cells were enriched from the spleens of mice with B cell conditional deletion of LSD1, the cells were cultured for 3 days in the presence of OP9-DL1 cells and BAFF, and day 0 B220+CD93+ transitional B cells and day 3 B220+CD21+CD1d+ ex vivo-derived marginal zone B cells were FACS-sorted and RNA-seq was performed to identify LSD1-target regulated genes.

2019-08-06 | GSE132198 | GEO

Transcriptional Changes in Germinal Center (GC) B cells from LSD1 conditional knockout mice

Project description:Using RNA-seq we identified the gene expression changes in GC B cells from LSD1 wild-type or LSD1-deficient mice immunized with T cell dependent antigens (Sheep Red Blood cells)

2018-12-10 | GSE106417 | GEO

Transcriptional Changes in Germinal Center (GC) B cells from LSD1 conditional knockout mice

Project description:Transcriptional Changes in Germinal Center (GC) B cells from LSD1 conditional knockout mice

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Illumina microarray experiment on LSD1 deletion ES cell with Lsd1Lox/Δ3 and Lsd1Δ3/Δ3

Project description:Lysine specific demethylase 1 (LSD1), which demethylates mono- and di- methylated histone H3-Lys4 as part of a complex including CoREST and histone deacetylases (HDAC), is essential for embryonic development in the mouse beyond e6.5 days. Here, we demonstrate that LSD1 expression and therefore function, is restricted to the epiblast of the post- implantation embryo. Conditional deletion of LSD1 in mouse embryonic stem (ES) cells, in vitro counterpart of the epiblast, revealed a reduction in CoREST protein, a subsequent decrease in associated HDAC activity and a global increase in Histone H3 Lys56 acetylation. Despite this biochemical perturbation, LSD1 deleted ES cells proliferate normally and retain stem cell characteristics. Loss of LSD1 causes the aberrant expression of 588 genes, including a number of transcription factors with roles in tissue development such as brachyury, Hoxb7, Hoxd8 and RARγ. Brachyury, a key-regulator of mesodermal differentiation, is a direct target gene of LSD1 and is over-expressed in e6.5 day Lsd1 genetrap embryos. Thus, LSD1 is required for the appropriate expression of key developmental regulators, via the stabilization of the LSD1/CoREST/HDAC complex, during early embryonic development. RNA samples from Lsd1Lox/Δ3 and Lsd1Δ3/Δ3 cells were compared, three biological replicates were performed.

2010-12-06 | E-GEOD-21131 | biostudies-arrayexpress

Determination of Lsd1 function in inguinal white adipose tissue (ingWAT) by global transcriptome analysis

Project description:To investigate the role of Lsd1 in ingWAT we crossed mice harboring conditional Lsd1 alleles (Zhu et al., 2014) with the Adipoq-Cre deleter strain (Eguchi et al., 2011), which results in Cre-mediated loss of Lsd1 selectively in adipocytes. Transciptome analysis of ingWAT obtained from control and knock-out mice revealed 727 genes differentially expressed between Lsd1 knock-out and control mice at 6 weeks of age (p-value<10-2).

2017-08-22 | GSE93293 | GEO

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