Differentiation of transplanted haematopoietic stem cells tracked by single-cell transcriptomic analysis
Differentiation of transplanted haematopoietic stem cells tracked by single-cell transcriptomic analysis
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通过单细胞转录组分析追踪移植造血干细胞的分化
DOI：
10.1038/s41556-020-0512-1
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发表时间：
2020-05-04
影响因子：
21.3
通讯作者：
Cheng, Tao
中科院分区：
文献类型：
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作者：
Dong, Fang;Hao, Sha;Cheng, Tao
由于技术限制，尚未研究移植的造血干细胞（hsc）在进入预处理宿主后的表现。在这里，使用单细胞RNA测序，我们首先获得了28种造血细胞类型的基于转录组的分类。然后，我们将其与功能测定相结合，追踪移植后第一周内照射受体中免疫表型纯化的造血干细胞的动态变化。根据我们的转录分类，大多数骨髓和脾脏的造血干细胞成为多能祖细胞，偶尔，一些造血干细胞产生巨核红细胞或髓细胞前体。平行的体外和体内功能实验支持了在第一周内没有大量HSC扩增的强劲分化范式。因此，本研究揭示了造血干细胞在清髓受体早期移植的动力学和命运选择，对造血干细胞和其他干细胞的临床应用具有重要意义。
How transplanted haematopoietic stem cells (HSCs) behave soon after they reside in a preconditioned host has not been studied due to technical limitations. Here, using single-cell RNA sequencing, we first obtained the transcriptome-based classifications of 28 haematopoietic cell types. We then applied them in conjunction with functional assays to track the dynamic changes of immunophenotypically purified HSCs in irradiated recipients within the first week after transplantation. Based on our transcriptional classifications, most homed HSCs in bone marrow and spleen became multipotent progenitors and, occasionally, some HSCs gave rise to megakaryocytic–erythroid or myeloid precursors. Parallel in vitro and in vivo functional experiments supported the paradigm of robust differentiation without substantial HSC expansion during the first week. Therefore, this study uncovers the previously inaccessible kinetics and fate choices of transplanted HSCs in myeloablated recipients at early stage, with implications for clinical applications of HSCs and other stem cells.