Multi-species tomo-sequencing identifies new major hematopoietic stem cell regulators in the microenvironment of the embryonic aorta

The behavior of (stem) cells is regulated by their local microenvironment through biochemical and biophysical interactions. To advance our understanding of the molecular characteristics and key components of the microenvironment, we applied a genome-wide RNA tomography sequencing approach in zebrafish, chicken, mouse and human embryos. The resulting anterior-posterior and/or dorsal-ventral transcriptional maps provide a powerful resource for identifying and comparing expression patterns in a given tissue or microenvironment along the embryonic axes of multiple species. We used these maps to explore the regulatory function of the aortic microenvironment, where the first hematopoietic stem cells are generated during embryonic development. By performing inter-species comparative analyses, we identified and functionally validated new conserved regulators of hematopoietic stem cell generation. Further analysis of spatial transcriptomics will elucidate the regulatory functions of the local microenvironment in vivo, paving the way for improved (stem) cell production in vitro and clinical cell therapy. Spatial transcriptomics by RNA-tomography (Tomo-seq) on whole or sub-dissected embryos (processed along the anterior-to-posterior axis) and on transversal thick slices (processed along the dorsal-to-ventral axis).（干）细胞的行为受其局部微环境通过生物化学与生物物理相互作用调控。为深化对微环境分子特征与核心组分的认知，我们在斑马鱼、鸡、小鼠及人类胚胎中应用了全基因组RNA层析测序（RNA tomography sequencing，Tomo-seq）技术。由此获得的前后轴及/或背腹轴转录图谱，可为多物种胚胎轴上特定组织或微环境的基因表达模式识别与比对提供极具价值的研究资源。 我们依托上述图谱探究了主动脉微环境的调控功能——胚胎发育过程中首批造血干细胞正是在此处产生。通过跨物种比较分析，我们鉴定并功能验证了一批全新的保守型造血干细胞生成调控因子。对空间转录组（Spatial transcriptomics）的进一步解析将阐明局部微环境的体内调控功能，为体外优化（干）细胞制备及临床细胞治疗奠定基础。 本数据集的空间转录组数据通过RNA层析测序（Tomo-seq）获取，样本涵盖完整胚胎或解剖分离的亚胚胎组织（沿前后轴处理）以及沿背腹轴制备的横向厚切片。