Donor age and C1orf132/MIR29B2C determine age-related methylation signature of blood after allogeneic hematopoietic stem cell transplantation.
Our recent study demonstrated that DNA methylation status in a set of CpGs located in ELOVL2, C1orf132, TRIM59, KLF14, and FHL2 can accurately predict calendar age in blood. In the present work, we used these markers to evaluate the effect of allogeneic hematopoietic stem cell transplantation (HSCT) on the age-related methylation signature of human blood.



DNA methylation in 32 CpGs was investigated in 16 donor-recipient pairs using pyrosequencing. DNA was isolated from the whole blood collected from recipients 27-360 days (mean 126) after HSCT and from the donors shortly before the HSCT.



It was found that in the recipients, the predicted age did not correlate with their calendar age but was correlated with the calendar age (r = 0.94, p = 4 × 10(-8)) and predicted age (r = 0.97, p = 5 × 10(-10)) of a respective donor. Despite this strong correlation, the predicted age of a recipient was consistently lower than the predicted age of a donor by 3.7 years (p = 7.8 × 10(-4)). This shift was caused by hypermethylation of the C1orf132 CpGs, for C1orf132 CpG_1. Intriguingly, the recipient-donor methylation difference correlated with calendar age of the donor (r = 0.76, p = 6 × 10(-4)). This finding could not trivially be explained by shifts of the major cellular factions of blood.



We confirm the single previous report that after HSCT, the age of the donor is the major determinant of age-specific methylation signature in recipient's blood. A novel finding is the unique methylation dynamics of C1orf132 which encodes MIR29B2C implicated in the self-renewing of hematopoietic stem cells. This observation suggests that C1orf132 could influence graft function after HSCT.
Biology Department, Central Forensic Laboratory of the Police, Warsaw, 00-583 Poland.
Magdalena
M
Spólnicka
Biology Department, Central Forensic Laboratory of the Police, Warsaw, 00-583 Poland.
Renata Zbieć
RZ
Piekarska
L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, 53-114 Poland ; Lower Silesian Center for Cellular Transplantation with National Bone Marrow Donor Registry, Wroclaw, 53-439 Poland.
Emilia
E
Jaskuła
Department of Hematology, Oncology and Internal Diseases, The Medical University of Warsaw, Warsaw, 02-097 Poland.
Grzegorz W
GW
Basak
Department of Forensic Medicine, Medical and Forensic Genetics Laboratory, Medical University of Lodz, Lodz, 91-304 Poland.
Renata
R
Jacewicz
Biology Department, Central Forensic Laboratory of the Police, Warsaw, 00-583 Poland.
Agnieszka
A
Pięta
Biology Department, Central Forensic Laboratory of the Police, Warsaw, 00-583 Poland.
Żanetta
Ż
Makowska
Department of Forensic Medicine, Medical and Forensic Genetics Laboratory, Medical University of Lodz, Lodz, 91-304 Poland.
Maciej
M
Jedrzejczyk
Department of Hematology, Medical University of Lodz, Copernicus Memorial Hospital, Lodz, 93-510 Poland.
Agnieszka
A
Wierzbowska
Department of Hematology, Medical University of Lodz, Copernicus Memorial Hospital, Lodz, 93-510 Poland.
Agnieszka
A
Pluta
Department of Hematology, Medical University of Lodz, Copernicus Memorial Hospital, Lodz, 93-510 Poland.
Tadeusz
T
Robak
Department of Forensic Medicine, Medical and Forensic Genetics Laboratory, Medical University of Lodz, Lodz, 91-304 Poland.
Jarosław
J
Berent
Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, 30-387 Poland.
Wojciech
W
Branicki
Department of Hematology, Oncology and Internal Diseases, The Medical University of Warsaw, Warsaw, 02-097 Poland.
Wiesław
W
Jędrzejczak
Lower Silesian Center for Cellular Transplantation with National Bone Marrow Donor Registry, Wroclaw, 53-439 Poland.
Andrzej
A
Lange
Department of Medical Genetics, Warsaw Medical University, Pawińskiego 3c, Warsaw, PL 02-106 Poland.
Rafał
R
Płoski
D019175:DNA Methylation; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D014019:Tissue Donors
Aging; Allogeneic hematopoietic stem cell transplantation; DNA methylation; MIR29B2C; Rejuvenation