期刊
STEM CELL REPORTS
卷 16, 期 7, 页码 1705-1717出版社
CELL PRESS
DOI: 10.1016/j.stemcr.2021.05.019
关键词
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资金
- Swedish Research Council
- Swedish Cancer Foundation
- Swedish Pediatric Cancer Foundation
- Knut och Alice Wallenbergs Stiftelse
- European Research Council (ERC) under the European Union [648894]
- HematoLinne program at Lund University
- StemTherapy program at Lund University
- European Research Council (ERC) [648894] Funding Source: European Research Council (ERC)
Genetic deletion of Gata2 allows efficient conditioning of recipient HSCs for transplantation without irradiation, leading to robust engraftment of donor HSCs. Different modes and timings of recipient conditioning can influence the functional features of transplanted HSCs.
Hematopoietic stem cells (HSCs) are typically characterized by transplantation into irradiated hosts in a highly perturbed microenvironment. Here, we show that selective and temporally controlled depletion of resident HSCs through genetic deletion of Gata2 constitutes efficient recipient conditioning for transplantation without irradiation. Strikingly, we achieved robust engraftment of donor HSCs even when delaying Gata2 deletion until 4 weeks after transplantation, allowing homing and early localization to occur in a completely nonperturbed environment. When HSCs from the congenic strains Ly5.1 and Ly5.2 were competitively transplanted, we found that the more proliferative state of Ly5.2 HSCs was associated with superior long-term engraftment when using conditioning by standard irradiation, while higher CXCR4 expression and a better homing ability of Ly5.1 HSCs strongly favored the outcome in our inducible HSC depletion model. Thus, the mode and timing of recipient conditioning challenges distinct functional features of transplanted HSCs.
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