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Uncoupling key determinants of hematopoietic stem cell engraftment through cell-specific and temporally controlled recipient conditioning

Miharada, Natsumi LU ; Rydström, Anna LU ; Rak, Justyna LU and Larsson, Jonas LU (2021) In Stem Cell Reports 16(7). p.1705-1717
Abstract

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 non-perturbed 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... (More)

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 non-perturbed 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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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cxcr4, engraftment, Gata2, hematopoietic stem cells, transplantation
in
Stem Cell Reports
volume
16
issue
7
pages
13 pages
publisher
Cell Press
external identifiers
  • scopus:85109448044
  • pmid:34171287
ISSN
2213-6711
DOI
10.1016/j.stemcr.2021.05.019
language
English
LU publication?
yes
id
5a18cd91-20ac-44b1-bcbd-a8e13755ab58
date added to LUP
2021-08-18 22:54:10
date last changed
2024-06-15 14:40:21
@article{5a18cd91-20ac-44b1-bcbd-a8e13755ab58,
  abstract     = {{<p>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 non-perturbed 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.</p>}},
  author       = {{Miharada, Natsumi and Rydström, Anna and Rak, Justyna and Larsson, Jonas}},
  issn         = {{2213-6711}},
  keywords     = {{Cxcr4; engraftment; Gata2; hematopoietic stem cells; transplantation}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{7}},
  pages        = {{1705--1717}},
  publisher    = {{Cell Press}},
  series       = {{Stem Cell Reports}},
  title        = {{Uncoupling key determinants of hematopoietic stem cell engraftment through cell-specific and temporally controlled recipient conditioning}},
  url          = {{http://dx.doi.org/10.1016/j.stemcr.2021.05.019}},
  doi          = {{10.1016/j.stemcr.2021.05.019}},
  volume       = {{16}},
  year         = {{2021}},
}