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The histone demethylase KDM2B regulates human primordial germ cell-like cells specification

ABSTRACT: The histone demethylase KDM2B regulates human primordial germ cell-like cells specification

PROVIDER: PRJNA675367 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13008809_1.fastq.gz	Fastqsanger.gz
	SRR13008809_2.fastq.gz	Fastqsanger.gz
	SRR13008810_1.fastq.gz	Fastqsanger.gz
	SRR13008810_2.fastq.gz	Fastqsanger.gz
	SRR13008811_1.fastq.gz	Fastqsanger.gz

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The histone demethylase KDM2B regulates human primordial germ cell-like cells specification

Project description:Germline specification is a fundamental step for human reproduction and this biological phenomenon possesses technical challenges to study in vivo as it occurs immediately after blastocyst implantation. The establishment of in vitro human primordial germ cell-like cells (hPGCLCs) induction system allows sophisticated characterization of human primordial germ cells (hPGCs) development. However, the underlying molecular mechanisms of hPGCLC specification are not fully elucidated. Here, we observed particularly high expression of the histone demethylase KDM2B in male fetal germ cells (FGCs) but not in male somatic cells. Besides, KDM2B shared similar expression pattern with hPGC marker genes in hPGCLCs, suggesting an important role of KDM2B in germ cell development. Although deletion of KDM2B had no significant effects on human embryonic stem cell (hESC)’s pluripotency, loss of KDM2B dramatically impaired hPGCLCs differentiation whereas ectopically expressed KDM2B could efficiently rescue such defect, indicating this defect was due to KDM2B’s loss in hPGCLC specification. Mechanistically, as revealed by the transcriptional profiling, KDM2B suppressed the expression of somatic genes thus inhibited somatic differentiation during hPGCLC specification. These data collectively indicate that KDM2B is an indispensable epigenetic regulator for hPGCLC specification, shedding lights on how epigenetic regulations orchestrate transcriptional events in hPGC development for future investigation.

2021-01-10 | GSE160287 | GEO

The histone demethylase KDM2B regulates human primordial germ cell-like cells specification.

Project description:Germline specification is a fundamental step for human reproduction and this biological phenomenon possesses technical challenges to study in vivo as it occurs immediately after blastocyst implantation. The establishment of in vitro human primordial germ cell-like cells (hPGCLCs) induction system allows sophisticated characterization of human primordial germ cells (hPGCs) development. However, the underlying molecular mechanisms of hPGCLC specification are not fully elucidated. Here, we observed particularly high expression of the histone demethylase KDM2B in male fetal germ cells (FGCs) but not in male somatic cells. Besides, KDM2B shared similar expression pattern with hPGC marker genes in hPGCLCs, suggesting an important role of KDM2B in germ cell development. Although deletion of KDM2B had no significant effects on human embryonic stem cell (hESC)'s pluripotency, loss of KDM2B dramatically impaired hPGCLCs differentiation whereas ectopically expressed KDM2B could efficiently rescue such defect, indicating this defect was due to KDM2B's loss in hPGCLC specification. Mechanistically, as revealed by the transcriptional profiling, KDM2B suppressed the expression of somatic genes thus inhibited somatic differentiation during hPGCLC specification. These data collectively indicate that KDM2B is an indispensable epigenetic regulator for hPGCLC specification, shedding lights on how epigenetic regulations orchestrate transcriptional events in hPGC development for future investigation.

| S-EPMC7893587 | biostudies-literature

Role of the histone demethylase KDM2B in hematopoietic homeostasis and malignancies [ChIP-seq]

Project description:Development of the hematopoietic system is dynamically controlled by the interplay of transcriptional and epigenetic networks to determine cellular identity. Those networks are critical for homeostasis and frequently dysregulated in leukemias. We identified histone demethylase Kdm2b as a critical regulator of definitive hematopoiesis and lineage specification of hematopoietic stem and progenitor cells (HSPCs). RNA sequencing in murine HSPCs and genome-wide chromatin immunoprecipitation studies in human leukemias revealed that Kdm2b regulates differentiation, lineage choice, cytokine signaling, and quiescence. Identify the binding of KDM2B in seven human leukemia cell lines

2016-02-22 | E-GEOD-70624 | biostudies-arrayexpress

Role of the histone demethylase KDM2B in hematopoietic homeostasis and malignancies [RNA-seq]

Project description:Development of the hematopoietic system is dynamically controlled by the interplay of transcriptional and epigenetic networks to determine cellular identity. Those networks are critical for homeostasis and frequently dysregulated in leukemias. We identified histone demethylase Kdm2b as a critical regulator of definitive hematopoiesis and lineage specification of hematopoietic stem and progenitor cells (HSPCs). RNA sequencing in murine HSPCs and genome-wide chromatin immunoprecipitation studies in human leukemias revealed that Kdm2b regulates differentiation, lineage choice, cytokine signaling, and quiescence. Comparison of gene expression in wild-type and knockout HSPCs

2016-02-22 | E-GEOD-70728 | biostudies-arrayexpress

Role of the histone demethylase KDM2B in hematopoietic homeostasis and malignancies [human cell line gene expression]

Project description:Development of the hematopoietic system is dynamically controlled by the interplay of transcriptional and epigenetic networks to determine cellular identity. Those networks are critical for homeostasis and frequently dysregulated in leukemias. We identified histone demethylase Kdm2b as a critical regulator of definitive hematopoiesis and lineage specification of hematopoietic stem and progenitor cells (HSPCs). RNA sequencing in murine HSPCs and genome-wide chromatin immunoprecipitation studies in human leukemias revealed that Kdm2b regulates differentiation, lineage choice, cytokine signaling, and quiescence. Identify the KDM2B dependent transcriptome in human leukemia cell lines by using the GeneChipÂ® PrimeViewâ¢ Human Gene Expression Array

2016-02-22 | E-GEOD-74959 | biostudies-arrayexpress

CRISPR screening in human primordial germ cell-like cells specification

Project description:CRISPR screening in human primordial germ cell-like cells specification

| PRJNA837979 | ENA

Role of the histone demethylase KDM2B in hematopoietic homeostasis and malignancies [RNA-seq]

2016-02-22 | GSE70728 | GEO

Role of the histone demethylase KDM2B in hematopoietic homeostasis and malignancies [ChIP-seq]

2016-02-22 | GSE70624 | GEO

Role of the histone demethylase KDM2B in hematopoietic homeostasis and malignancies [Kras background mouse gene expression]

Project description:Development of the hematopoietic system is dynamically controlled by the interplay of transcriptional and epigenetic networks to determine cellular identity. Those networks are critical for homeostasis and frequently dysregulated in leukemias. We identified histone demethylase Kdm2b as a critical regulator of definitive hematopoiesis and lineage specification of hematopoietic stem and progenitor cells (HSPCs). RNA sequencing in murine HSPCs and genome-wide chromatin immunoprecipitation studies in human leukemias revealed that Kdm2b regulates differentiation, lineage choice, cytokine signaling, and quiescence. Comparison of gene expression in wild-type and knockout HSPCs We analyzed lineage depleted cells isolated from bone marrow from mice that express oncogenic Kras in the context of knockout and overexpression of Kdm2b in Affymetrxi GeneChipÂ® Mouse Gene 2.0 ST Array

2016-02-22 | E-GEOD-74960 | biostudies-arrayexpress

KDM2B is a Histone H3K79 Demethylase and Induces Transcriptional Repression via SIRT1-mediated Chromatin Silencing

Project description:The methylation of histone H3 lysine 79 (H3K79) acts as an active chromatin marker and is enriched in actively transcribed regions of the genome. However, demethylase of this mark remains unknown despite intensive research. Here, we show that KDM2B (FBXL10), a member of the Jumonji C (JmjC) family of proteins and previously known for its histone H3K36 demethylase activity, is a di- and trimethyl H3K79 demethylase. We demonstrate that KDM2B induces transcriptional repression of HOXA7 and MEIS1 via occupancy of promoters and demethylation of H3K79. Furthermore, genome-wide analysis suggests that H3K79 methylation levels are increased when KDM2B is depleted, suggesting that KDM2B functions as an H3K79 demethylase in vivo. Finally, stable KDM2B-knockdown cell lines exhibited displacement of SIRT1, with concomitant increases in H3K79 methylation and H4K16 acetylation. Our findings identify KDM2B as an H3K79 demethylase and link its function to transcriptional repression via SIRT1-mediated chromatin silencing.

2017-10-21 | GSE89052 | GEO

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