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Series GSE202817 Query DataSets for GSE202817
Status Public on Jan 03, 2025
Title ZBTB16/PLZF regulates self-renewal and differentiation of spermatogonial stem cells through an extensive transcription factor-chromatin poising network [RNA-Seq]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Spermatogonial stem cells (SSCs) balance self-renewal versus differentiation/spermatogenesis to ensure continuous sperm production. Here, we uncover multiple roles for the transcription factor ZBTB16/PLZF in juvenile mouse undifferentiated spermatogonia (uSPG). ZBTB16 activates genes in uSPG promoting self-renewal and cell cycle progression (Ccnd1) to maintain uSPG and transit-amplifying states. Remarkably, in uSPG, ZBTB16, SALL4, SOX3 all co-localize at over 12,000 promoters regulating uSPG and meiosis. These regions also feature broad H3K4me3 and H3K27ac marks, DNA hypomethylation, and often CTCF binding. Hi-C analyses reveal robust promoter-promoter physical interactions, revealing a transcription factor and higher-order active chromatin interaction network within uSPG that poises meiotic promoters for subsequent activation. Conversely, these factors do not occupy germline-specific promoters driving spermiogenesis, which instead lack promoter-promoter physical interactions and bear DNA hypermethylation. Therefore, ZBTB16 ensures uSPG cell cycle progression and colocalizes with SALL4, SOX3 and often CTCF to establish a novel chromatin poising network.Spermatogonial stem cells (SSCs) balance self-renewal and differentiation to ensure continuous sperm production in the testis. The transcription factor Zbtb16 (PLZF) supports undifferentiated SSC maintenance through partly unknown mechanisms. We combined genomics (RNA-seq and ChIP-seq) and genetic approaches to reveal multiple functions of Zbtb16 in juvenile mouse SSCs. Zbtb16-bound loci show a striking correlation with active promoters bearing H3K4me3 and the activator Sall4. Zbtb16 activates genes that support SSC self-renewal and cell cycle progression (e.g., Ccnd1) that help maintain undifferentiated SSC pools, including both self-renewing SSCs and transit-amplifying progenitors. Zbtb16 also attenuates certain genes, including meiotic genes and specific retrotransposons that confer genome instability. Notably, Zbtb16 genome localization and its impact on the transcriptome are dynamic, displaying mesenchymal gene targets in vivo, which are not maintained in cultured SSCs. Our data reveal dynamic roles for Zbtb16 in ensuring SSC identity, amplification, and maintenance in vivo.
 
Overall design To better understand Zbtb16 function in vivo, we isolated SSCs and then performed RNA-seq and histone modification ChIP-seq. We also performed ChIP-seq for the transcription factors Zbtb16 and Sall4 using whole testis to reveal directly regulated genes in postnatal mouse spermatogonia.
 
Contributor(s) Yi C, Cairns BR
Citation(s) 40033150
Submission date May 12, 2022
Last update date Mar 04, 2025
Contact name Bradley R. Carins
E-mail(s) brad.cairns@hci.utah.edu
Phone 8015851822
Organization name University of Utah
Department Oncological Sciences
Lab Cairns Lab
Street address 2000 Circle of Hope
City Salt Lake City
State/province UT
ZIP/Postal code 84112
Country USA
 
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (24)
GSM6133808 RNAseq_THY1+_uSPG_Zbtb16_WT_rep1
GSM6133809 RNAseq_KIT+_dSPG_Zbtb16_WT_rep1
GSM6133810 RNAseq_THY1+_uSPGs_Zbtb16_Null_rep1
This SubSeries is part of SuperSeries:
GSE202819 ZBTB16/PLZF regulates juvenile spermatogonial stem cell development via an extensive transcription factor poising network
Relations
BioProject PRJNA837421

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Supplementary file Size Download File type/resource
GSE202817_RNAseq.FPKM.txt.gz 1.7 Mb (ftp)(http) TXT
GSE202817_RNAseq.Sox3.FPKM.txt.gz 1.6 Mb (ftp)(http) TXT
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