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Androgen Promotes Differentiation of Promyelocytic Leukemia Zinc Finger (PLZF)+ Spermatogonia pool via Indirect Regulatory Pattern

ABSTRACT: Androgen Promotes Differentiation of Promyelocytic Leukemia Zinc Finger (PLZF)+ Spermatogonia pool via Indirect Regulatory Pattern

PROVIDER: PRJEB28167 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR2733130.fastq.gz	Fastqsanger.gz
	ERR2733128.fastq.gz	Fastqsanger.gz
	ERR2733129.fastq.gz	Fastqsanger.gz

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Androgen Promotes Differentiation of Promyelocytic Leukemia Zinc Finger (PLZF)+ Spermatogonia pool via Indirect Regulatory Pattern

Project description:We examined a regulatory role of the AR during the process of spermatogenesis. Using a SSCs-Sertoli cells co-culture system, we demonstrated that androgen negatively regulated Plzf in SSCs that co-exist with Sertoli cells. In addition, we identified Gata2 as a target of AR in Sertoli cells, and subsequently observed that Wilms tumor 1 (WT1) and β1-integrin as two putative intermediate molecules to transfer the differentiation signals to SSCs. This signal pathway was further verified using androgen pharmacological deprivation mice model. These results demonstrate a regulatory pattern of androgen in SSCs niche, that androgen turns off the stemness maintenance switch PLZF in undifferentiated spermatogonia populations to promote spermatogenesis in an indirect way via multiple steps of signal transduction.

2019-02-28 | E-MTAB-7129 | biostudies-arrayexpress

PLZF & SALL4 ChIP-seq in undifferentiated spermatogonia

Project description:Cultured THY1+ spermatogonia were used to reveal the genomic targets of PLZF and SALL4 in undifferentiated spermatogonia.

2016-04-19 | GSE73390 | GEO

PLZF and DDX5 interacting proteins in spermatogonia

Project description:DDX5, or PLZF co-immunoprecipitation in lysates from cultured undifferentiated spermatogonia followed by identification of eluted proteins using mass spectrometry. IgG control IPs included.

2019-02-24 | MSV000083476 | MassIVE

Androgen promotes differentiation of PLZF<sup>+</sup> spermatogonia pool via indirect regulatory pattern.

Project description:BackgroundAndrogen plays a pivotal role in spermatogenesis, accompanying a question how androgen acts on germ cells in testis since germ cells lack of androgen receptors (AR). Promyelocytic leukemia zinc-finger (PLZF) is essential for maintenance of undifferentiated spermatogonia population which is terminologically called spermatogonia progenitor cells (SPCs).AimsWe aim to figure out the molecular connections between androgen and fates of PLZF+ SPCs population.MethodImmunohistochemistry was conducted to confirm that postnatal testicular germ cells lacked endogenous AR. Subsequently, total cells were isolated from 5 dpp (day post partum) mouse testes, and dihydrotestosterone (DHT) and/or bicalutamide treatment manifested that Plzf was indirectly regulated by androgen. Then, Sertoli cells were purified to screen downstream targets of AR using ChIP-seq, and gene silence and overexpression were used to attest these interactions in Sertoli cells or SPCs-Sertoli cells co-culture system. Finally, these connections were further verified in vivo using androgen pharmacological deprivation mouse model.ResultsGata2 is identified as a target of AR, and β1-integrin is a target of Wilms' tumor 1 (WT1) in Sertoli cells. Androgen signal negatively regulate β1-integrin on Sertoli cells via Gata2 and WT1, and β1-integrin on Sertoli cells interacts with E-cadherin on SPCs to regulate SPCs fates.ConclusionAndrogen promotes differentiation of PLZF+ spermatogonia pool via indirect regulatory pattern.

| S-EPMC6542041 | biostudies-literature

The Promyelocytic Leukemia Zinc Finger Transcription Factor (PLZF) is Critical for Human Endometrial Stromal Cell Decidualization

Project description:Whole genome binding profile of PLZF in human endometrial stromal cells (hESCs)

2016-03-09 | GSE75115 | GEO

Transcription profiling of human U937T:PLZF-RARa Inducible Cells

Project description:The PLZF-RARa fusion oncoprotein is overexpressed in the t(11;17) subtype of acute promyelocytic leukemia. Gene expression microarrays were used to identify genes involved in leukemic transformation. We used microarray to detect gene expression changes induced by the PLZF-RARa fusion oncoprotein in the U937 cell line Experiment Overall Design: The U937T:PLZF-RARa cell line was engineered to express PLZF-RARa upon tetracycline removal. PLZF-RARa was induced for 48hr and RNA was extracted and hybridized to Affymetrix HGU133Plus2.0 Chips

2009-12-05 | E-GEOD-18476 | biostudies-arrayexpress

Gene Expression Data from U937T:PLZF-RARa Inducible Cells

2009-11-30 | GSE18476 | GEO

Identification of EOMES-expressing spermatogonial stem cells and their regulation by PLZF

Project description:Long-term maintenance of spermatogenesis in mammals is supported by GDNF, an essential growth factor required for spermatogonial stem cell (SSC) self-renewal. Exploiting a transgenic GDNF overexpression model, which expands and normalizes the pool of undifferentiated spermatogonia between Plzf +/+ and Plzf lu/lu mice, we used RNAseq to identify a rare subpopulation of cells that express EOMES, a T-box transcription factor. Lineage tracing, conditional ablation, and busulfan challenge show that these are long-term SSCs that contribute to steady state spermatogenesis as well as regeneration following chemical injury. EOMES+ SSCs have a lower proliferation index than EOMES− GFRA1+ spermatogonia in wild-type but not in Plzf lu/lu mice. This comparison demonstrates that PLZF regulates their proliferative activity and suggests that EOMES+ SSCs are lost through proliferative exhaustion in Plzf lu/lu mice. Single cell RNA sequencing of EOMES+ cells from Plzf +/+ and Plzf lu/lu mice support a hierarchical model of a slow-cycling long-term SSC population supporting more rapid-cycling short-term SSCs.

2019-05-30 | GSE116001 | GEO

PLZF limits enhancer activity during hematopoietic progenitor aging

Project description:PLZF (promyelocytic leukemia zinc finger) is a transcription factor acting as a global regulator of hematopoietic commitment. PLZF displays an epigenetic specificity by recruiting chromatin-modifying factors but little is known about its role in remodeling chromatin of cells committed towards a given specific hematopoietic lineage. In murine myeloid progenitors, we decipher a new role for PLZF in restraining active genes and enhancers by targeting acetylated lysine 27 of Histone H3 (H3K27ac). Functional analyses reveal that active enhancers bound by PLZF are involved in biological processes related to metabolism and associated with hematopoietic aging. Comparing the epigenome of young and old myeloid progenitors, we reveal that H3K27ac variation at active enhancers is a hallmark of hematopoietic aging. Taken together, these data suggest that PLZF, associated with active enhancers, appears to restrain their activity as an epigenetic gatekeeper of hematopoietic aging.

2018-12-21 | GSE124190 | GEO

Regulation of the positive transcriptional effect of PLZF through a non-canonical EZH2 activity

Project description:The transcription factor PLZF (promyelocytic leukemia zinc finger protein) acts as an epigenetic regulator balancing self-renewal and differentiation of hematopoietic cells through binding to various chromatin-modifying factors. First described as a transcriptional repressor, PLZF is also associated with active transcription, although the molecular bases underlying the differences are unknown. Here, we reveal that, in a hematopoietic cell line, PLZF is predominantly associated with transcribed genes. Additionally, we identify a new association between PLZF and the histone methyltransferase, EZH2 at the genomic level. We find that co-occupancy of PLZF and EZH2 on chromatin at PLZF target genes is not associated with SUZ12 or trimethylated lysine 27 of histone H3 (H3K27me3) but with the active histone mark H3K4me3 and active transcription. Removal of EZH2 leads to an increase of PLZF binding and increased in gene expression. Our results suggest a new role of EZH2 in restricting PLZF positive transcriptional activity independently of its canonical PRC2 activity.

2018-01-26 | GSE109619 | GEO

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