Characterization of organ-level specification of murine vascular endothelial cells from embryonic-stage to post-puberty adulthood.

Vascular endothelial cells (ECs) establish via paracrine signaling tissue-specific niches that promote organ revascularization and regeneration. Given these executive functions, transplantation of ECs into the vasculature has been used to stimulate organ repair. However, challenges in faithfully deriving tissue-specific endothelium within in vitro culture conditions limit large-scale expansion potential, long-term functional stability, and the cell homing and engraftment potential towards the target organ. Identification of the transcriptional regulators that modulate the specification of generic or unspecified endothelial cell populations into tissue-specific vascular ECs may provide novel factors to be incorporated into standard stem-cell differentiation protocols. Such controlled expression of the appropriate angiocrine factors--in combination with the niche microenvironment--could support the necessary crosstalk and cell-to-cell membrane interactions necessary for positioning and anastomosis when transplanted. Previously, investigation of the transcriptome profiles of ECs originating from diverse vascular beds has helped identify potential transcriptional regulators and gene markers of EC tissue specification. We aim to expand on these studies by elaborating on the progression of EC tissue specification as it occurs from embryonic development to adulthood. A better understanding of how ECs acquire their tissue specificity and deconvolution of the transient expression patterns of key molecular regulators could provide crucial information on the establishment of EC tissue-specific function which can then be recapitulated in vitro. Our long-term goal is to generate transcriptionally stable and functional tissue-specific ECs from stem-cell derived EC banks suitable for transplantation for the purpose of promoting non-fibrotic tissue regeneration after organ injury. Expression profiling by high throughput sequencing data; GPL21103 Illumina HiSeq 4000 (Mus musculus).血管内皮细胞（vascular endothelial cells，ECs）通过旁分泌信号通路构建组织特异性龛位，以促进器官血管重建与再生。鉴于其上述核心调控功能，将ECs移植入血管系统已被用于刺激器官修复。然而，在体外培养条件下精准获取组织特异性内皮细胞所面临的诸多挑战，限制了其大规模扩增潜力、长期功能稳定性，以及向靶器官归巢与定植的能力。鉴定能够调控普通或未特化内皮细胞群体向组织特异性血管内皮细胞分化的转录调控因子，可为纳入标准干细胞分化方案提供全新的调控靶点。在与龛位微环境联合应用的前提下，精准表达合适的血管分泌因子，可维持移植所需的细胞间串扰与细胞膜相互作用，以保障细胞定植与血管吻合形成。此前，针对不同血管床来源的ECs转录组谱的研究，已助力鉴定出调控ECs组织特化的潜在转录调控因子与基因标志物。本研究旨在拓展此类研究，系统解析ECs组织特化从胚胎发育到成年的完整动态进程。深入阐明ECs获得组织特异性的机制，并解析关键分子调控因子的瞬时表达模式，可为明确ECs组织特异性功能的建立机制提供关键依据，进而实现在体外对该过程的重现。本研究的长期目标是从干细胞来源的内皮细胞库中获取转录稳定且功能完整的组织特异性ECs，以用于器官损伤后促进非纤维化组织再生的移植治疗。本数据集通过高通量测序技术开展表达谱分析；数据集采用GPL21103平台，基于Illumina HiSeq 4000测序，实验对象为小家鼠（Mus musculus）。