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Series GSE64960 Query DataSets for GSE64960
Status Public on Feb 27, 2015
Title Sexual cell fate reprogramming in the ovary by DMRT1
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Transcription factors related to the insect sex determination gene Doublesex (DMRT proteins) control sex determination and/or sexual differentiation in diverse metazoans. They also are implicated in transitions between sex-determining mechanisms during vertebrate evolution. In mice Dmrt1 is required for male gonadal differentiation in somatic cells and germ cells. DMRT1 also maintains male gonadal sex: its loss, even in adults, can trigger sexual fate reprogramming in which male Sertoli cells transdifferentiate into their female equivalents - granulosa cells - and testicular tissue reorganizes to a more ovarian morphology. Here we use a conditional Dmrt1 transgene to show that Dmrt1 is not only necessary but also sufficient to specify male cell identity in the mouse gonad. DMRT1 expression in the ovary silenced the female sex-maintenance gene Foxl2 and reprogrammed juvenile and adult granulosa cells into Sertoli-like cells, triggering formation of structures resembling male seminiferous tubules. DMRT1 can silence Foxl2 even in the absence of the testis-determining genes Sox8 and Sox9. mRNA profiling found that DMRT1 activates many testicular genes and downregulates ovarian genes and single cell RNA-seq in transdifferentiating cells identified dynamically expressed candidate mediators of this process. Strongly upregulated genes were highly enriched on chromosome X, consistent with sexually antagonistic functions. This study provides an in vivo example of single gene reprogramming of cell sexual identity. Our findings suggest a reconsideration of mechanisms involved in human disorders of sexual development (DSD) and empirically support evolutionary models where loss or gain of Dmrt1 function promotes establishment of new vertebrate sex determination systems.
 
Overall design RNA-Seq (3 conditions, 2 replicates per condition) and Single Cell RNA-Seq (68 individual cells and 1 bulk cell sample)
Web link https://github.com/micahgearhart/cag-dmrt1
 
Contributor(s) Zarkower D, Gearhart M
Citation(s) 25683803
Submission date Jan 14, 2015
Last update date May 15, 2019
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)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
GPL16417 Illumina MiSeq (Mus musculus)
Samples (144)
GSM1585048 WT Male Replicate 1
GSM1585049 WT Male Replicate 2
GSM1585050 WT Female Replicate 1
Relations
BioProject PRJNA272586
SRA SRP052224

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
GSE64960_8-10week_gonad_counts.csv.gz 363.3 Kb (ftp)(http) CSV
GSE64960_RAW.tar 964.5 Mb (http)(custom) TAR (of BIGWIG)
GSE64960_single_cell_counts.csv.gz 789.0 Kb (ftp)(http) CSV
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record
Processed data provided as supplementary file
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