Comprehensive Single-Cell Multiomics Analysis Reveals Gene Regulatory Networks Underlying Sex Determination in Murine Primordial Germ Cells

Khái niệm cốt lõi

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.

Tóm tắt

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.

Thống kê

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.

Trích dẫn

"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."

Thông tin chi tiết chính được chắt lọc từ

Single-nucleus multiomics reveals the gene-regulatory networks underlying sex determination of murine primordial germ cells

by Alexander,A.... lúc www.biorxiv.org 02-21-2024

https://www.biorxiv.org/content/10.1101/2024.02.19.581036v2

Yêu cầu sâu hơn

How do the gene regulatory networks identified in this study compare across different mammalian species?

The gene regulatory networks identified in this study provide valuable insights into the molecular mechanisms underlying sex determination of murine primordial germ cells (PGCs). While specific transcription factors such as TFAP2c, TCFL5, GATA2, MGA, NR6A1, TBX4, and ZFX were found to be enriched in XX PGCs, and the forkhead-box and POU6 families of transcription factors were observed in XY PGCs, it is essential to note that these networks may exhibit variations across different mammalian species. Evolutionary divergence and species-specific regulatory elements could lead to differences in the gene regulatory networks governing PGC development and sex determination. Comparative studies across various mammalian species, including humans, could help elucidate conserved pathways and species-specific adaptations in PGC development.

What are the potential implications of disrupting the key transcription factor pathways or signaling cascades in PGC sex determination?

Disrupting key transcription factor pathways or signaling cascades involved in primordial germ cell (PGC) sex determination could have profound implications for sexual reproduction and fertility. Transcription factors play a crucial role in regulating the expression of sexually dimorphic genes in PGCs, ultimately determining whether PGCs differentiate into oogenic or spermatogenic lineages. Disruption of these pathways could lead to improper lineage commitment, resulting in developmental abnormalities, infertility, or even sex reversal in individuals.
Furthermore, perturbing signaling cascades such as WNT, BMP, and RA signaling, which were found to be temporally expressed during PGC sex determination, could impact the communication between supporting cells and PGCs. This disruption may interfere with the proper guidance and differentiation of PGCs, affecting gametogenesis and reproductive potential. Understanding the consequences of disrupting these key pathways is crucial for developing targeted interventions to correct abnormalities in PGC development and improve fertility outcomes.

Could the insights from this study on PGC development be leveraged to improve in vitro gametogenesis or fertility treatments?

The insights gained from this study on primordial germ cell (PGC) development, including the identification of gene regulatory networks, transcription factors, and signaling pathways involved in PGC sex determination, hold significant promise for improving in vitro gametogenesis and fertility treatments. By understanding the molecular mechanisms that drive PGC lineage commitment and differentiation, researchers can potentially optimize culture conditions and differentiation protocols to enhance the efficiency and success of in vitro gametogenesis.
Targeting key transcription factors or signaling cascades identified in this study could be leveraged to manipulate PGC fate in vitro, guiding their development towards desired gametic lineages. This knowledge could also inform the development of novel therapeutic strategies for individuals with fertility issues stemming from PGC developmental defects. By applying the findings from this study, researchers may pave the way for more effective and personalized fertility treatments, ultimately benefiting individuals seeking assisted reproductive technologies.