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.

中文翻译：

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通过单细胞转录组分析跟踪移植的造血干细胞的分化。

由于技术限制，尚未研究移植的造血干细胞 (HSC) 在预调节宿主中后不久的行为。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，我们将它们与功能测定结合使用，以跟踪移植后第一周内受辐射受体中免疫表型纯化的 HSC 的动态变化。根据我们的转录分类，骨髓和脾脏中的大多数归巢 HSC 成为多能祖细胞，偶尔，一些 HSC 会产生巨核细胞-红细胞或骨髓前体。平行的体外和体内功能实验支持在第一周内没有大量 HSC 扩增的稳健分化范式。