Taz protects hematopoietic stem cells from an aging-dependent decrease in PU.1 activity

Hematopoietic stem cells (HSC) - the unique tissue-specific stem cells in the bone marrow - are responsible for maintaining the stem cell pool and replenishing all types of blood cells in a lifetime. The balance between differentiation and self-renewal potential of HSC is essential to maintain immune balance. HSCs gradually lose their regenerative potential, and produce fewer lymphoid cells during aging. Although old HSCs show a functional decline, they still maintain minimal functionality. I uncovered a protective role of TAZ in HSCs during aging. TAZ plays a transcriptional coactivator of PU.1 which is a key regulator of the HSC function. Upregulated TAZ buffers an age-associated decline of PU.1 activity to maintain a minimal regenerative potential. In addition, I found an aging surface marker “Clca3a1” that is a proxy for the TAZ activity. Old LT-HSCs are heterogenous consisting of “true” aged HSCs and “young-like” HSCs. We anticipate that these findings provide a better understanding of HSC aging and contribute to uncovering a future therapeutic target for HSC rejuvenation.