An Erratic Gene Expression Signature in Primary Hematopoietic Stem Cells: Implications for Interpretations of Aging

A decline in hematopoietic stem cell (HSC) function is believed to underlie hematological shortcomings with age, but a comprehensive molecular understanding of these changes is currently lacking. Here, we provide evidence that a transcriptional signature reported in several prior studies on HSC aging is linked to stress-induced changes in gene expression rather than aging. Our findings have strong implications for the design and interpretation of HSC aging studies. Overall design: Single cell RNA-sequencing was performed to determine the immediate early response signature among hematopoietic stem and progenitor cells in response to different cell isolation protocols. The technology was coupled to cell hashing in order to measure the data simultaneously in samples treated with different conditions.