Conceitos Básicos
Integrative single-nucleus multiomics profiling of chromatin accessibility and gene expression uncovers the gene regulatory networks that govern sex determination in murine primordial germ cells.
Resumo
The study presents a comprehensive single-nucleus multiomics analysis of murine primordial germ cells (PGCs) during embryonic development. The researchers developed a single-cell sequencing approach to simultaneously profile chromatin accessibility and gene expression in XX and XY PGCs.
Key insights:
The study resolved previously unreported PGC subpopulations and generated a multimodal reference atlas of differentiating PGC clusters.
Regulatory element accessibility precedes gene expression during PGC development, suggesting chromatin accessibility primes PGC lineage commitment.
Sexual dimorphism in chromatin accessibility and gene expression increases over time in PGCs.
The researchers computationally mapped the transcription factor networks regulating sexually dimorphic genes in PGCs. XX PGCs showed enrichment for factors like TFAP2c, TCFL5, GATA2, while XY PGCs were enriched for forkhead-box and POU6 families.
The study also identified temporal patterns of WNT, BMP, and RA signaling pathways during PGC sex determination, and potential new cell communication pathways between PGCs and supporting cells.
Overall, the findings provide comprehensive insights into the gene regulatory mechanisms underlying sex determination in murine primordial germ cells.
Estatísticas
Primordial germ cells (PGCs) are the bipotential precursors of mature gametes that commit to an oogenic or spermatogenic fate in response to sex-determining cues from the fetal gonad.
The critical processes required for PGCs to integrate and respond to signals from the somatic environment in gonads are not fully understood.
Citações
"Accurate specification of female and male germ cells during embryonic development is critical for sexual reproduction."
"Combining single-nucleus sequencing data, we computationally mapped the cohort of transcription factors that regulate the expression of sexually dimorphic genes in PGCs."
"Our results illustrate the diversity of factors involved in programming PGCs towards a sex-specific fate."