| First Author | Flohr Svendsen A | Year | 2021 |
| Journal | Blood | Volume | 138 |
| Issue | 6 | Pages | 439-451 |
| PubMed ID | 33876187 | Mgi Jnum | J:315674 |
| Mgi Id | MGI:6829540 | Doi | 10.1182/blood.2020009729 |
| Citation | Flohr Svendsen A, et al. (2021) A comprehensive transcriptome signature of murine hematopoietic stem cell aging. Blood 138(6):439-451 |
| abstractText | We surveyed 16 published and unpublished data sets to determine whether a consistent pattern of transcriptional deregulation in aging murine hematopoietic stem cells (HSC) exists. Despite substantial heterogeneity between individual studies, we uncovered a core and robust HSC aging signature. We detected increased transcriptional activation in aged HSCs, further confirmed by chromatin accessibility analysis. Unexpectedly, using 2 independent computational approaches, we established that deregulated aging genes consist largely of membrane-associated transcripts, including many cell surface molecules previously not associated with HSC biology. We show that Selp (P-selectin), the most consistent deregulated gene, is not merely a marker for aged HSCs but is associated with HSC functional decline. Additionally, single-cell transcriptomics analysis revealed increased heterogeneity of the aged HSC pool. We identify the presence of transcriptionally "young-like" HSCs in aged bone marrow. We share our results as an online resource and demonstrate its utility by confirming that exposure to sympathomimetics or deletion of Dnmt3a/b molecularly resembles HSC rejuvenation or aging, respectively. |
