Prolonged generation of multi-lineage blood cells in wild-type animals from pluripotent stem cells.
Prolonged generation of multi-lineage blood cells in wild-type animals from pluripotent stem cells.
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DOI：
10.1016/j.stemcr.2023.01.009
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发表时间：
2023-03-14
影响因子：
5.9
通讯作者：
Wang, Jinyong
中科院分区：
文献类型：
--
作者：
Peng, Huan;Lin, Yunqing;Hu, Fangxiao;Lv, Cui;Wu, Bingyan;Weng, Qitong;Liu, Lijuan;Xia, Chengxiang;Liu, Xiaofei;Zhao, Yalan;Zhang, Qi;Geng, Yang;Zhang, Mengyun;Wang, Jinyong
从多能干细胞（PSC）再生延长的多谱系造血，无限的细胞来源，是再生血液学的一个重要目标。在这项研究中，我们使用了基因编辑的PSC系，并揭示了三种转录因子Runx 1，Hoxa 9和Hoxa 10的同时表达，推动了诱导造血祖细胞（iHPC）的强劲出现。iHPC在野生型动物中成功移植，并重新增殖了丰富和完整的髓系、B系和T系成熟细胞。生殖性多谱系造血在多个器官中正常分布，持续6个月以上，并最终随时间下降，无白血病发生。在单细胞分辨率下的生成性骨髓细胞、B细胞和T细胞的转录组表征进一步将它们的身份投射到天然细胞对应物。因此，我们提供的证据表明，外源Runx 1，Hoxa 9和Hoxa 10的共表达同时导致使用PSC衍生的iHPC作为细胞来源的骨髓，B和T谱系的长期重建。iR 1A 9A 10-ESC衍生的iHPC在野生型动物中产生多谱系血细胞产生的多谱系细胞显示出多器官分布的特征诱导谱系细胞在转录水平上类似于其天然对应物诱导祖细胞在次级受体中显示出长期重建能力在这篇文章中，Wang及其同事表明，外源Runx 1，Hoxa 9，并且Hoxa 10引导mESC向造血祖细胞分化，其移植可靠地重建了野生型动物中延长的多种血细胞，包括骨髓细胞、B细胞和T细胞。该研究提供了使用PSC来源重建生殖造血的见解。
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. iR1A9A10-ESC-derived iHPCs generate multi-lineage blood cells in wild-type animals Generative multi-lineage cells show features of multi-organ distribution Induced-lineage cells resemble their natural counterparts at the transcription level Induced progenitors show long-term reconstitution capacity in secondary recipients In this article, Wang and colleagues show that combinational expression of exogenous Runx1, Hoxa9, and Hoxa10 guides mESC differentiation toward hematopoietic progenitors, transplantation of which reliably reconstitutes prolonged multiple blood cells, including myeloid cells, B cells, and T cells in wild-type animals. The study provides insights into reconstituting generative hematopoiesis using a PSC source.
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影响因子：
64.8
作者：
Chen, Michael J.;Yokomizo, Tomomasa;Zeigler, Brandon M.;Dzierzak, Elaine;Speck, Nancy A.
通讯作者：
Speck, Nancy A.
影响因子：
8
作者：
Collins CT;Hess JL
通讯作者：
Hess JL
影响因子：
5.7
作者：
Bruschi, Michela;Vanzolini, Tania;Sahu, Neety;Balduini, Alessandra;Magnani, Mauro;Fraternale, Alessandra
通讯作者：
Fraternale, Alessandra
影响因子：
7.3
作者：
De Kleer I;Willems F;Lambrecht B;Goriely S
通讯作者：
Goriely S
影响因子：
4.3
作者：
Bhatlekar S;Fields JZ;Boman BM
通讯作者：
Boman BM