Decoding the Universal Human Chromatin Landscape through Teratoma-Based Profiling [Multiome]

Teratoma formation is key for evaluating differentiation of human pluripotent stem cells into embryonic germ layers and serves as a model for understanding stem cell differentiation and developmental processes. Its potential for insights into epigenome and transcriptome profiling is significant. This study integrates the analysis of the epigenome and transcriptome of hESC-generated teratomas, comparing transcriptomes between hESCs and teratomas. It employs cell type-specific expression patterns from single-cell data to deconvolve RNA-Seq data and identify cell types within teratomas. Our results provide a catalog of activating and repressive histone modifications, while also elucidating distinctive features of chromatin states. Construction of an epigenetic signature matrix enabled the quantification of diverse cell populations in teratomas and enhanced the ability to unravel the epigenetic landscape in heterogeneous tissue contexts. This study also includes a single cell multiome atlas of expression (scRNA-Seq) and chromatin accessibility (scATAC-Seq) of human teratomas, further revealing the complexity of these tissues. A histology-based digital staining tool further complemented the annotation of cell types in teratomas, enhancing our understanding of their cellular composition. This research is a valuable resource for examining teratoma epigenomic and transcriptomic landscapes and serves as a model for epigenetic data comparison. Single-Nuclei Multiome (ATAC + Gene Expression) Sequencing of teratomas generated from H1 hESCs

畸胎瘤（Teratoma）形成是评估人类多能干细胞向胚胎胚层分化的核心手段，同时也是解析干细胞分化与发育进程的经典模型，在表观基因组（epigenome）与转录组（transcriptome）谱分析领域具备重要的研究价值。本研究整合了人类胚胎干细胞（human embryonic stem cells, hESC）来源畸胎瘤的表观基因组与转录组分析，对比了人类胚胎干细胞与畸胎瘤的转录组特征。研究采用单细胞数据中的细胞类型特异性表达模式，对RNA测序（RNA-Seq）数据进行解卷积，以识别畸胎瘤内的细胞类型。本研究结果不仅提供了激活型与抑制型组蛋白修饰（histone modifications）的完整编目，还阐明了染色质状态（chromatin states）的独特特征。构建的表观遗传特征矩阵可实现畸胎瘤中多种细胞群的定量分析，且提升了在异质性组织环境中解析表观遗传图谱的能力。本研究还涵盖了人类畸胎瘤的单细胞多组学图谱，包含单细胞RNA测序（scRNA-Seq，single-cell RNA Sequencing）与单细胞转座酶可及性测序（scATAC-Seq，single-cell assay for transposase-accessible chromatin sequencing），进一步揭示了这类组织的复杂性。一款基于组织学的数字化染色工具进一步辅助了畸胎瘤的细胞类型注释，加深了我们对其细胞组成的认知。本研究为探究畸胎瘤的表观基因组与转录组图谱提供了宝贵的研究资源，同时也可作为表观遗传数据对比分析的模型。本研究包含了由H1人类胚胎干细胞所生成畸胎瘤的单细胞核多组学（ATAC+基因表达）测序数据。