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Series GSE208106 Query DataSets for GSE208106
Status Public on Sep 30, 2022
Title Genomics of sexual cell fate transdifferentiation in the mouse gonad
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Other
Genome binding/occupancy profiling by high throughput sequencing
Summary Sex determination in mammals hinges on a cell fate decision in the fetal bipotential gonad between male Sertoli cells and female granulosa cells. While this decision normally is permanent, loss of key cell fate regulators such as the transcription factors Dmrt1 and Foxl2 can cause postnatal transdifferentiation from Sertoli to granulosa-like or vice versa. Here we examine the mechanism of transdifferentiation in mice carrying either a null mutation of Dmrt1 or a point mutation, R111G, that alters the DNA binding motif and causes human XY gonadal dysgenesis and sex reversal. We first define genes misexpressed during transdifferentiation and then show that female transcriptional regulators driving transdifferentiation in the mutant XY gonad (ESR2, LRH1, FOXL2) bind chromatin sites related to those normally bound in the XX ovary. We then define gene expression changes at the onset of transdifferentiation and abnormal chromatin compartments that may help destabilize cell fate and initiate transdifferentiation. We model the R111G mutation in mice and show that it causes dominant gonadal dysgenesis, analogous to its human phenotype but less severe. We show that R111G partially feminizes the testicular transcriptome and causes dominant disruption of DMRT1 binding specificity in vivo. These data help illuminate how transdifferentiation occurs when sexual cell fate maintenance is disrupted and identify chromatin sites and transcripts that may play key roles in the transdifferentiation process.
 
Overall design RNA-seq (30 samples), ChIP-seq (17 samples, and Hi-C (2 samples) on gonads and purified Sertoli cells.
 
Contributor(s) Zarkower D, Gearhart MD
Citation(s) 36200842
Submission date Jul 13, 2022
Last update date Dec 16, 2022
Contact name Micah Gearhart
E-mail(s) gearh006@umn.edu
Organization name University of Minnesota
Department Genetics, Cell Biology and Development
Street address 6-160 Jackson Hall, 321 Church St.
City Minneapolis
State/province MN
ZIP/Postal code 55455
Country USA
 
Platforms (2)
GPL21103 Illumina HiSeq 4000 (Mus musculus)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (51)
GSM6337374 RNA-seq of Dmrt1 +/+ P28 Gonad rep 1
GSM6337375 RNA-seq of Dmrt1 +/+ P28 Gonad rep 2
GSM6337376 RNA-seq of Dmrt1 +/+ P28 Gonad rep 3
Relations
BioProject PRJNA858398

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE208106_AB_Compartments_Dmrt1_null_null_p7_Sertoli.bigWig 2.5 Mb (ftp)(http) BIGWIG
GSE208106_DMRT1_ChIP_Dmrt1_R111G_null_p28_XY_gonad.bigWig 205.4 Mb (ftp)(http) BIGWIG
GSE208106_DMRT1_ChIP_Dmrt1_R111G_wt_p28_XY_gonad.bigWig 199.3 Mb (ftp)(http) BIGWIG
GSE208106_DMRT1_ChIP_Dmrt1_WT_null_p28_XY_gonad.bigWig 204.2 Mb (ftp)(http) BIGWIG
GSE208106_DMRT1_ChIP_Dmrt1_null_null_p28_XY_gonad.bigWig 115.6 Mb (ftp)(http) BIGWIG
GSE208106_Gene_Expression_Count_Table.csv.gz 1.5 Mb (ftp)(http) CSV
GSE208106_HiC_interactions_Dmrt1_null_null_p7_Sertoli.bedpe.gz 46.1 Kb (ftp)(http) BEDPE
GSE208106_RAW.tar 1.1 Gb (http)(custom) TAR (of BIGWIG)
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Processed data provided as supplementary file
Processed data are available on Series record
Raw data are available in SRA
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