4DNESXR4J4MS - Replicate experiments of RNA-seq on RUES2 differentiated to mesoderm

Vascular endothelial cells are a mesoderm-derived lineage with many essential functions, including angiogenesis and coagulation. The gene-regulatory mechanisms underpinning endothelial specialization are largely unknown, as are the roles of chromatin organization in regulating endothelial cell transcription. To investigate the relationships between chromatin organization and gene expression, we induced endothelial cell differentiation from human pluripotent stem cells and performed Hi-C and RNA-sequencing assays at specific time points. Long-range intrachromosomal contacts increase over the course of differentiation, accompanied by widespread heteroeuchromatic compartment transitions that are tightly associated with transcription. Dynamic topologically associating domain boundaries strengthen and converge on an endothelial cell state, and function to regulate gene expression. Chromatin pairwise point interactions (DNA loops) increase in frequency during differentiation and are linked to the expression of genes essential to vascular biology. Chromatin dynamics guide transcription in endothelial cell development and promote the divergence of endothelial cells from cardiomyocytes. Overall design: lab: Chuck Murry, UW award: 1U54DK107979-01 accession: 4DNESXR4J4MS condition: mesoderm - day 2 submitted_by: Kris Alavattam dataset_label: RNA-seq on human iPSCs differentiated to endothelium contributing_labs: William Noble, UW experiment_type: RNA-seq url: https://data.4dnucleome.org/experiment-set-replicates/4DNESXR4J4MS/ number_of_experiments: 2 experiment: 4DNEXNQUX8R8; replicate_number: Biorep 1, Techrep 1 experiment: 4DNEXV26Q4OX; replicate_number: Biorep 2, Techrep 1

血管内皮细胞（vascular endothelial cells）是一类源自中胚层（mesoderm）的细胞谱系，具备诸多核心生理功能，包括血管生成（angiogenesis）与凝血调控（coagulation）。目前学界对支撑内皮细胞特化的基因调控机制，以及染色质组织（chromatin organization）在调控内皮细胞转录（transcription）过程中的作用仍知之甚少。
为探究染色质组织与基因表达之间的关联，本研究通过人多能干细胞（human pluripotent stem cells）诱导分化为内皮细胞，并在特定时间节点开展Hi-C与RNA测序（RNA-sequencing）实验检测。
分化过程中，长范围染色体内相互作用（long-range intrachromosomal contacts）频次逐渐升高，同时伴随广泛的异染色质-常染色质区室转换（heteroeuchromatic compartment transitions），该转换与转录过程紧密相关。动态的拓扑关联结构域（topologically associating domain, TAD）边界逐渐强化，并向内皮细胞状态收敛，进而发挥调控基因表达的功能。染色质成对位点相互作用（即DNA环，DNA loops）的发生频率在分化过程中逐步提升，并与血管生物学核心基因的表达密切相关。染色质动态变化调控内皮细胞发育过程中的转录过程，并推动内皮细胞与心肌细胞（cardiomyocytes）的谱系分化。
整体实验设计：
实验负责人：Chuck Murry，华盛顿大学（UW）
项目资助编号：1U54DK107979-01
数据入库编号：4DNESXR4J4MS
实验条件：中胚层 - 第2天
提交人：Kris Alavattam
数据集标签：人诱导多能干细胞（induced pluripotent stem cells, iPSCs）向内皮细胞分化的RNA测序实验
合作实验室：William Noble，华盛顿大学（UW）
实验类型：RNA测序（RNA-seq）
数据链接：https://data.4dnucleome.org/experiment-set-replicates/4DNESXR4J4MS/
实验数量：2
实验1：4DNEXNQUX8R8；生物学重复1，技术重复1
实验2：4DNEXV26Q4OX；生物学重复2，技术重复1