Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH, Bethesda, MD, USA.
Biodata Mining and Discovery Section, NIAMS, NIH, Bethesda, MD, USA.
Cell Rep. 2022 Aug 16;40(7):111219. doi: 10.1016/j.celrep.2022.111219.
Embryonic stem cells (ESCs) can adopt lineage-specific gene-expression programs by stepwise exposure to defined factors, resulting in the generation of functional cell types. Bulk and single-cell-based assays were employed to catalog gene expression, histone modifications, chromatin conformation, and accessibility transitions in ESC populations and individual cells acquiring a presomitic mesoderm fate and undergoing further specification toward myogenic and neurogenic lineages. These assays identified cis-regulatory regions and transcription factors presiding over gene-expression programs occurring at defined ESC transitions and revealed the presence of heterogeneous cell populations within discrete ESC developmental stages. The datasets were employed to identify previously unappreciated genomic elements directing the initial activation of Pax7 and myogenic and neurogenic gene-expression programs. This study provides a resource for the discovery of genomic and transcriptional features of pluripotent, mesoderm-induced ESCs and ESC-derived cell lineages.
胚胎干细胞（ESCs）可以通过逐步暴露于定义的因子来采用谱系特异性的基因表达程序，从而产生功能性细胞类型。使用批量和单细胞为基础的检测方法来对 ESC 群体和单个细胞的基因表达、组蛋白修饰、染色质构象和可及性转变进行编目，这些细胞获得了体节中胚层命运，并进一步向肌源性和神经源性谱系特化。这些检测方法鉴定了顺式调控区域和转录因子，它们控制着在特定 ESC 转变过程中发生的基因表达程序，并揭示了在离散的 ESC 发育阶段内存在异质细胞群体。这些数据集被用于鉴定以前未被认识的基因组元件，这些元件指导 Pax7 以及肌源性和神经源性基因表达程序的初始激活。本研究为发现多能性、中胚层诱导的 ESCs 以及 ESC 衍生的细胞谱系的基因组和转录特征提供了资源。
