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Abstract：
BACKGROUND: The Pharyngeal Endoderm (PE) is an extremely relevant developmental tissue, serving as the progenitor for the esophagus, parathyroids, thyroids, lungs, and thymus. While several studies have highlighted the importance of PE cells, a detailed transcriptional and epigenetic characterization of this important developmental stage is still missing, especially in humans, due to technical and ethical constraints pertaining to its early formation.
RESULTS: Here we fill this knowledge gap by developing an in vitro protocol for the derivation of PE-like cells from human Embryonic Stem Cells (hESCs) and by providing an integrated multi-omics characterization. Our PE-like cells robustly express PE markers and are transcriptionally homogenous and similar to in vivo mouse PE cells. In addition, we define their epigenetic landscape and dynamic changes in response to Retinoic Acid by combining ATAC-Seq and ChIP-Seq of histone modifications. The integration of multiple high-throughput datasets leads to the identification of new putative regulatory regions and to the inference of a Retinoic Acid-centered transcription factor network orchestrating the development of PE-like cells.
CONCLUSIONS: By combining hESCs differentiation with computational genomics, our work reveals the epigenetic dynamics that occur during human PE differentiation, providing a solid resource and foundation for research focused on the development of PE derivatives and the modeling of their developmental defects in genetic syndromes.
RESULTS: Here we fill this knowledge gap by developing an in vitro protocol for the derivation of PE-like cells from human Embryonic Stem Cells (hESCs) and by providing an integrated multi-omics characterization. Our PE-like cells robustly express PE markers and are transcriptionally homogenous and similar to in vivo mouse PE cells. In addition, we define their epigenetic landscape and dynamic changes in response to Retinoic Acid by combining ATAC-Seq and ChIP-Seq of histone modifications. The integration of multiple high-throughput datasets leads to the identification of new putative regulatory regions and to the inference of a Retinoic Acid-centered transcription factor network orchestrating the development of PE-like cells.
CONCLUSIONS: By combining hESCs differentiation with computational genomics, our work reveals the epigenetic dynamics that occur during human PE differentiation, providing a solid resource and foundation for research focused on the development of PE derivatives and the modeling of their developmental defects in genetic syndromes.
摘要：
背景：咽内胚层（PE）是一种极其相关的发育组织，作为食道的祖先，甲状旁腺,甲状腺,肺,还有胸腺.虽然一些研究强调了PE细胞的重要性，这一重要发育阶段的详细转录和表观遗传特征仍然缺失，尤其是在人类中，由于其早期形成的技术和道德限制。
结果：在这里，我们通过开发从人类胚胎干细胞（hESC）衍生PE样细胞的体外方案，并通过提供综合的多组学表征来填补这一知识空白。我们的PE样细胞强健地表达PE标志物,并且在转录上是同质的,并且与体内小鼠PE细胞相似。此外,我们通过结合ATAC-Seq和ChIP-Seq组蛋白修饰来定义它们的表观遗传景观和响应维甲酸的动态变化。多个高通量数据集的整合导致新的推定调控区的鉴定和以视黄酸为中心的转录因子网络的推断，从而协调PE样细胞的发育。
结论：通过将hESCs分化与计算基因组学相结合，我们的工作揭示了人类PE分化过程中发生的表观遗传动力学，为专注于PE衍生物的开发及其在遗传综合征中的发育缺陷建模的研究提供了坚实的资源和基础。
结果：在这里，我们通过开发从人类胚胎干细胞（hESC）衍生PE样细胞的体外方案，并通过提供综合的多组学表征来填补这一知识空白。我们的PE样细胞强健地表达PE标志物,并且在转录上是同质的,并且与体内小鼠PE细胞相似。此外,我们通过结合ATAC-Seq和ChIP-Seq组蛋白修饰来定义它们的表观遗传景观和响应维甲酸的动态变化。多个高通量数据集的整合导致新的推定调控区的鉴定和以视黄酸为中心的转录因子网络的推断，从而协调PE样细胞的发育。
结论：通过将hESCs分化与计算基因组学相结合，我们的工作揭示了人类PE分化过程中发生的表观遗传动力学，为专注于PE衍生物的开发及其在遗传综合征中的发育缺陷建模的研究提供了坚实的资源和基础。
