CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou 510530, China; University of Chinese Academy of Sciences, Beijing 100049, China.
University of Chinese Academy of Sciences, Beijing 100049, China; State Key Laboratory of Stem Cell and Reproductive Biology, Institute for Stem Cell and Regeneration, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Stem Cell Reports. 2023 Mar 14;18(3):720-735. doi: 10.1016/j.stemcr.2023.01.009. Epub 2023 Feb 16.
Regenerating prolonged multi-lineage hematopoiesis from pluripotent stem cells (PSCs), an unlimited cell source, is a crucial aim of regenerative hematology. In this study, we used a gene-edited PSC line and revealed that simultaneous expression of three transcription factors, Runx1, Hoxa9, and Hoxa10, drove the robust emergence of induced hematopoietic progenitor cells (iHPCs). The iHPCs engrafted successfully in wild-type animals and repopulated abundant and complete myeloid-, B-, and T-lineage mature cells. The generative multi-lineage hematopoiesis distributed normally in multiple organs, persisted over 6 months, and eventually declined over time with no leukemogenesis. Transcriptome characterization of generative myeloid, B, and T cells at the single-cell resolution further projected their identities to natural cell counterparts. Thus, we provide evidence that co-expression of exogenous Runx1, Hoxa9, and Hoxa10 simultaneously leads to long-term reconstitution of myeloid, B, and T lineages using PSC-derived iHPCs as the cell source.
从多能干细胞（PSCs）中再生长期多谱系造血，作为一种无限的细胞来源，是再生血液学的一个关键目标。在这项研究中，我们使用了一种基因编辑的 PSC 系，并揭示了同时表达三种转录因子，Runx1、Hoxa9 和 Hoxa10，可驱动诱导造血祖细胞（iHPCs）的大量出现。iHPCs 成功植入野生型动物体内，并重新填充了大量和完整的骨髓细胞、B 细胞和 T 细胞谱系成熟细胞。生成的多谱系造血在多个器官中正常分布，持续超过 6 个月，最终随着时间的推移逐渐减少，没有白血病发生。在单细胞分辨率下对生成性骨髓、B 和 T 细胞的转录组特征进行进一步分析，预测了它们与天然细胞对应物的身份。因此，我们提供了证据表明，同时表达外源 Runx1、Hoxa9 和 Hoxa10 可利用 PSC 衍生的 iHPCs 作为细胞来源，长期重建骨髓细胞、B 细胞和 T 细胞谱系。
