Differentiation of haematopoietic stem cells upon transplantation tracked by single cell transcriptomics

How transplanted haematopoietic stem cells (HSCs) reside and behave in a preconditioned host at the early stage has not been studied due to technical limitations. Here, by single-cell RNA-sequencing, we first obtained the transcriptome-based classifications of 28 haematopoietic cell types, and then applied them in conjunction with functional assays to track the dynamic changes of highly purified HSCs in irradiated recipients within the first week after transplantation. Based on our transcriptional classifications, most homed HSCs in bone marrow and spleen were shown to become 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 vigorous 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.