PDF(Pubmed)
Abstract：
PU.1 (SPI1) is pivotal in hematopoiesis, yet its role in human endothelial-to-hematopoietic transition (EHT) remains unclear. Comparing human in vivo and in vitro EHT transcriptomes revealed SPI1\'s regulatory role. Knocking down SPI1 during in vitro EHT led to a decrease in the generation of hematopoietic progenitor cells (HPCs) and their differentiation potential. Through multi-omic analysis, we identified KLF1 and LYL1 - transcription factors specific to erythroid/myeloid and lymphoid cells, respectively - as downstream targets of SPI1. Overexpressing KLF1 or LYL1 partially rescues the SPI1 knockdown-induced reduction in HPC formation. Specifically, KLF1 overexpression restores myeloid lineage potential, while LYL1 overexpression re-establishes lymphoid lineage potential. We also observed a SPI1-LYL1 axis in the regulatory network in in vivo EHT. Taken together, our findings shed new light on the role of SPI1 in regulating lineage commitment during EHT, potentially contributing to the heterogeneity of hematopoietic stem cells (HSCs).
摘要：
PU.1（SPI1）在造血中至关重要，然而,其在人内皮-造血细胞转化(EHT)中的作用尚不清楚.比较人体内和体外EHT转录组揭示了SPI1的调节作用。在体外EHT过程中敲除SPI1导致造血祖细胞（HPCs）的生成及其分化潜力降低。通过多元分析，我们鉴定了KLF1和LYL1-红细胞/骨髓和淋巴样细胞特异性转录因子，分别作为SPI1的下游目标。过表达KLF1或LYL1部分挽救了SPI1敲低诱导的HPC形成减少。具体来说,KLF1过表达可恢复髓系潜能，而LYL1过表达重新建立淋巴谱系潜能。我们还在体内EHT的调节网络中观察到SPI1-LYL1轴。一起来看,我们的发现为SPI1在EHT期间调节谱系承诺的作用提供了新的思路，可能导致造血干细胞（HSC）的异质性。
