Hematopoeitic Stem Cells and Their Progenitors Critically Require Autophagy to Promote Early Engraftment Following Allogeneic Stem Cell Transplantation
| العنوان: | Hematopoeitic Stem Cells and Their Progenitors Critically Require Autophagy to Promote Early Engraftment Following Allogeneic Stem Cell Transplantation |
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| المؤلفون: | Geoffrey R. Hill, Laetitia Le Texier, Lucie Leveque-El Mouttie, Kelli P. A. MacDonald, Rachel D. Kuns, Bianca E. Teal, Katie E. Lineburg |
| المصدر: | Blood. 126:34-34 |
| بيانات النشر: | American Society of Hematology, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Myeloid, medicine.medical_treatment, Immunology, ATG5, Cell Biology, Hematology, Hematopoietic stem cell transplantation, Biology, Biochemistry, Transplantation, Haematopoiesis, surgical procedures, operative, medicine.anatomical_structure, medicine, Bone marrow, Progenitor cell, Stem cell |
| الوصف: | Stem cell transplantation (SCT) is the only curative therapy for the majority of hematological malignancies and relies on successful engraftment of donor hematopoietic stem cells (HSC) to reconstitute the patient's hematopoiesis and immunity. Graft-versus-host disease (GVHD) and graft failure are complications of SCT that contribute to significant morbidity and mortality. Recent studies have established a role for autophagy in the long-term survival and function of HSCs and as a regulator of hematopoiesis. We investigated the contribution of autophagy to HSC in the setting of allogeneic transplantation. Using LC3-GFP bone marrow as a graft source in the well-established B6 into F1 model of GVHD, together with imaging flow cytometry, we demonstrated increased autophagy (LC3-GFP punctae) within donor HSC and progenitor cells in GVHD compared to non-GVHD recipients. To assess the contribution of autophagy to HSC development and function we used mice deficient in Atg5, an essential protein for the autophagy pathway. In primary transplants, ATG5 KO foetal liver (FL) had reduced ability to engraft lethally irradiated congenic recipient mice compared to WT FL. Furthermore, competitive transplantation of 50% ATG5 KO FL cells together with 50% WT FL cells demonstrated that ATG5 KO cells had a reduced capacity to reconstitute compared to congenic WT FL cells. Finally, to address the role of autophagy in HSC in the setting of GVHD, we transplanted WT or ATG5 KO FL ± T cells into lethally irradiated B6D2F1 recipients. At D10 post-transplant ATG5 KO recipients failed to establish tri-lineage engraftment in peripheral blood and lacked expansion of myeloid precursor cells in the BM, leading to engraftment failure and significantly reduced survival compared to WT FL recipients (50% WT vs 10% Atg5 KO p Disclosures No relevant conflicts of interest to declare. |
| تدمد: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.v126.23.34.34 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::d5894673207e51c116891b1d67d901ca https://doi.org/10.1182/blood.v126.23.34.34 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi...........d5894673207e51c116891b1d67d901ca |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15280020 00064971 |
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| DOI: | 10.1182/blood.v126.23.34.34 |