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Uncoupling key dete...
Uncoupling key determinants of hematopoietic stem cell engraftment through cell-specific and temporally controlled recipient conditioning
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- Miharada, Natsumi (author)
- Lund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine
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- Rydström, Anna (author)
- Lund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine
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- Rak, Justyna (author)
- University of Cambridge
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- Larsson, Jonas (author)
- Lund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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(creator_code:org_t)
- Elsevier BV, 2021
- 2021
- English 13 s.
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In: Stem Cell Reports. - : Elsevier BV. - 2213-6711. ; 16:7, s. 1705-1717
- Related links:
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http://dx.doi.org/10... (free)
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http://www.cell.com/...
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Abstract
Subject headings
Close
- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
Keyword
- Cxcr4
- engraftment
- Gata2
- hematopoietic stem cells
- transplantation
Publication and Content Type
- art (subject category)
- ref (subject category)
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