A comprehensive transcriptome signature of murine hematopoietic stem cell aging

To determine whether a consistent pattern of transcriptional deregulation in aging murine hematopoietic stem cells (HSC) exists, we collected all available transcriptome studies of aged HSCs, adding our own unpublished data. Cross-validation of all datasets identified a core list of consistently differentially expressed genes; the HSC aging signature. Despite heterogeneity between individual studies, the aging signature is robust and has reached saturation. Our analysis also indicates that HSCs become transcriptionally activated upon aging. Unexpectedly, the signature consists largely of membrane-associated transcripts, including many cell surface molecules previously not associated with HSC biology. We validated that Selp, the top aging gene, is not only a marker for aged HSCs but is functionally involved in age-associated HSC functional decline. We share the aging signature as an online resource with the community and demonstrate its value by confirming that exposure to sympathomimetics, and deletion of Dnmt3a/b, molecularly resembles HSC rejuvenation or aging, respectively. HighlightsO_LIA meta-analysis of murine HSC transcriptomes identifies a robust aging signature; C_LIO_LIThe HSC aging signature is highly enriched for cell membrane-related transcripts; C_LIO_LIHSCs become transcriptionally activated upon aging. C_LIO_LIP-selectin functionally contributes to HSC aging C_LI