Human and Murine Hematopoietic Stem Cell Aging Is Associated with Functional Impairments and Intrinsic Megakaryocytic/Erythroid Bias
Alexandra Rundberg Nilsson
Shamit Soneji
Sofia Adolfsson
David Bryder
Cornelis Jan Pronk
10.1371/journal.pone.0158369
https://plos.figshare.com/articles/dataset/Human_and_Murine_Hematopoietic_Stem_Cell_Aging_Is_Associated_with_Functional_Impairments_and_Intrinsic_Megakaryocytic_Erythroid_Bias/3915087
<div><p>Aging within the human hematopoietic system associates with various deficiencies and disease states, including anemia, myeloid neoplasms and reduced adaptive immune responses. Similar phenotypes are observed in mice and have been linked to alterations arising at the hematopoietic stem cell (HSC) level. Such an association is, however, less established in human hematopoiesis and prompted us here to detail characteristics of the most primitive human hematopoietic compartments throughout ontogeny. In addition, we also attempted to interrogate similarities between aging human and murine hematopoiesis. Coupled to the transition from human cord blood (CB) to young and aged bone marrow (BM), we observed a gradual increase in frequency of candidate HSCs. This was accompanied by functional impairments, including decreased lymphoid output and reduced proliferative potential. Downstream of human HSCs, we observed decreasing levels of common lymphoid progenitors (CLPs), and increasing frequencies of megakaryocyte/erythrocyte progenitors (MEPs) with age, which could be linked to changes in lineage-affiliated gene expression patterns in aged human HSCs. These findings were paralleled in mice. Therefore, our data support the notion that age-related changes also in human hematopoiesis involve the HSC pool, with a prominent skewing towards the megakaryocytic/erythroid lineages, and suggests conserved mechanisms underlying aging of the blood cell system.</p></div>
2016-07-01 17:54:32
BM
hematopoietic system associates
lymphoid progenitors
disease states
bone marrow
candidate HSCs
frequency
hematopoietic compartments
Murine Hematopoietic Stem Cell Aging
blood cell system
data support
cord blood
HSC pool
detail characteristics
CB
CLP
MEP
Similar phenotypes
Functional Impairments
lymphoid output
myeloid neoplasms
murine hematopoiesis
age-related changes
lineage-affiliated gene expression patterns