单细胞多组学在灵长类早期胚胎发育中的研究应用

Early Primate Embryo Development Meets Single-cell Multi-omics

啮齿类是研究胚胎发育的重要模型,然而啮齿类与灵长类在发育过程中存在巨大的种属差异,啮齿类中的研究并不能简单推广到灵长类中,因此灵长类生殖发育研究亟待开展。早期胚胎细胞数量稀少且复杂多样,通常采用单细胞测序技术来揭示其发育过程及调控机制。然而仅依靠单细胞单组学分析并不能有效全面地解析细胞间编码的复杂网络信息。单细胞多组学有效地联合转录组、表观遗传组、蛋白质组、代谢组等进行分析,使研究者能够在同一细胞水平上系统地解码不同细胞类型的异质性及发育轨迹,从多维度去理解灵长类早期胚胎发育的关键事件。本文总结了单细胞RNA治疗发展到多组学过程中关键技术的发展历程,并概述了多组学技术在深入解读灵长类早期胚胎发育研究中的应用及未来潜在的发展方向和挑战。

Given the constraints imposed by the“14-day ethics”rule,numerous critical events occurring between the second and fourth weeks of embryonic development remain poorly understood.This underscores the necessity of a detailed understanding of embryonic development and regulation during this period,which is indispensable for preventing pregnancy failure,treating birth defects,and promoting human reproductive health.Rodents,characterized by their small size,rapid growth,strong reproductive capacity,and fully sequenced genomes,are widely used as crucial models for studying embryonic development.However,the substantial physiological differences between rodents and primates due to evolutionary divergence make it challenging to directly apply findings from rodent studies to primates.Besides,primates,our closest relatives in terms of evolutionary phylogenetics and physiological characteristics,share more than 95%genetic homology with humans,underscoring the urgent need for primate research.Furthermore,early-stage embryonic cells are both scarce and diverse,making their regulatory mechanisms and developmental pathways typically elucidated through single-cell sequencing.For instance,three significant articles published in Science in 2018 mapped the complete atlas of organ and tissue development from fertilization and captured dynamic gene expression profiles in zebrafish and frogs through single-cell transcriptomics.Unfortunately,relying solely on single-cell omics analysis falls short in effectively and comprehensively deciphering the intricate cellular network information.Single-cell multi-omics empower researchers to systematically decode cell heterogeneity and developmental trajectories at the individual cell level by combining transcriptomics,epigenomics,proteomics,and metabolomics analyses.These emerging technologies play a significant role in life sciences,enabling the elucidation of critical early primate embryonic development events from a multi-dimensional perspective,including zygotic genome activation(ZGA),X-chromosome dosage compensation,origins of primordial germ cells(PGCs),mechanisms of cell fate determination,and pivotal events in gastrulation and early organogenesis.This article chronicles the advancement of pivotal technologies,from single-cell histology to multi-omics,beginning with the single-cell transcriptome and culminating in a comprehensive analysis according to the central dogma of molecular biology.It highlights the transition from a singular to a holistic perspective in cellular analysis and reviews the application of multi-omics techniques in unveiling early primate embryonic development.Finally,it delves into the application of multi-omics technologies in enhancing our understanding of early primate embryonic development and explores future possibilities,directions,and challenges in this rapidly evolving field.In doing so,it emphasizes the critical role of interdisciplinary approaches,combining insights from genetics,molecular biology,and bioinformatics to foster innovations in reproductive medicine and developmental biology.The integration of such technologies offers the promise of breakthroughs in understanding complex biological processes,potentially leading to novel therapeutic strategies and advancements in reproductive health and medicine.