Division of Life Science, State Key Laboratory of Molecular Neuroscience, Center of Systems Biology and Human Health, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong 999077, China.
Greater Bay Biomedical Innocenter, Shenzhen Bay Laboratory, Shenzhen Peking University, Hong Kong University of Science and Technology Medical Center, Shenzhen 518055, China.
Proc Natl Acad Sci U S A. 2022 Mar 29;119(13):e2119051119. doi: 10.1073/pnas.2119051119. Epub 2022 Mar 25.
SignificanceHematopoietic stem cells (HSCs) are generated from specialized endothelial cells, called hemogenic endothelial cells (HECs). It has been debated whether HECs and non-HSC-forming conventional endothelial cells (cECs) arise from a common precursor or represent distinct lineages. Moreover, the molecular basis underlying their distinct fate determination is poorly understood. We use photoconvertible labeling, time-lapse imaging, and single-cell RNA-sequencing analysis to trace the lineage of HECs. We discovered that HECs and cECs arise from a common hemogenic angioblast precursor, and their distinct fate is determined by high or low dosage of Etv2, respectively. Our results illuminate the lineage origin and a mechanism on the fate determination of HECs, which may enhance the understanding on the ontogeny of HECs in vertebrates.
意义造血干细胞（HSCs）来源于称为造血内皮细胞（HECs）的特殊内皮细胞。一直存在争议的是，HECs 和非造血形成常规内皮细胞（cECs）是否来自共同的前体，或者代表不同的谱系。此外，它们独特的命运决定的分子基础还知之甚少。我们使用光转化标记、延时成像和单细胞 RNA 测序分析来追踪 HEC 的谱系。我们发现 HECs 和 cECs 来源于共同的造血血管母细胞前体，它们的不同命运分别由 Etv2 的高或低剂量决定。我们的结果阐明了 HECs 的谱系起源和命运决定的机制，这可能有助于加深对脊椎动物 HECs 发生的理解。
