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Dmrt1 maintains testicular immune homeostasis by activating Spry1 and inhibiting NF-κB signaling pathway [ChIP-Seq]

ABSTRACT: In order to explore the mechanisms of Dmrt1 in regulating testicular immune homeostasis, we performed ChIP-seq analysis on primary SCs infected with a lentiviral vector expressing FLAG-tagged Dmrt1

ORGANISM(S): Capra hircus

PROVIDER: GSE212665 | GEO | 2023/09/01

REPOSITORIES: GEO

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Dmrt1 maintains testicular immune homeostasis by activating Spry1 and inhibiting NF-κB signaling pathway [Dmrt1 RNA-Seq]

Project description:To explore the potential function of Dmrt1 in spermatogenesis, we constructed a Dmrt1-deficiency mouse model by knockdown Dmrt1 in testicular seminiferous tubule specifically

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Dmrt1 maintains testicular immune homeostasis by activating Spry1 and inhibiting NF-κB signaling pathway [Spry1 KD RNA-Seq]

Project description:To explore the function of Spry1 in testis, we constructed a mouse model with testicular specific KD of Spry1 through seminiferous tubule transplantation

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Dmrt1 maintains testicular immune homeostasis by activating Spry1 and inhibiting NF-κB signaling pathway

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Sexual cell fate reprogramming in the ovary by DMRT1

Project description: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. RNA-Seq (3 conditions, 2 replicates per condition) and Single Cell RNA-Seq (68 individual cells and 1 bulk cell sample)

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