| Authors |
Chaudhary R, Cordova BA, Hong M, Klein BR, Contreras LA, Rashmil R, Goshevski F,
Smith JNP, Taylor DJ, Pieper AA, Markowitz S, Desai AB
|
| Submitted By |
Amar Desai on 9/24/2025 |
| Status |
Published |
| Journal |
Stem cells (Dayton, Ohio) |
| Year |
2025 |
| Date Published |
|
| Volume : Pages |
43 : Not Specified |
| PubMed Reference |
40608981 |
| Abstract |
Hematopoietic aging is characterized by diminished stem cell regenerative
capacity and an increased risk of hematologic dysfunction. We previously
identified that the prostaglandin-degrading enzyme 15-hydroxyprostaglandin
dehydrogenase (15-PGDH) regulates hematopoietic stem cell (HSC) activity. Here,
we expand on this work and demonstrate that in aged mice: (1) 15-PGDH expression
and activity remain conserved in the bone marrow (BM) and spleen, suggesting
that it remains a viable therapeutic target in aging; (2) prolonged PGDH
inhibition (PGDHi) significantly increases the frequency and number of
phenotypic hematopoietic stem and progenitor cells across multiple compartments,
with transcriptional changes indicative of enhanced function; (3) PGDHi-treated
BM enhances short-term hematopoietic recovery following transplantation, leading
to improved peripheral blood output and accelerated multilineage reconstitution;
and (4) PGDHi confers a competitive advantage in primary hematopoietic
transplantation while mitigating age-associated myeloid bias in secondary
transplants. Notably, these effects occur without perturbing steady-state blood
production, suggesting that PGDHi enhances hematopoiesis under regenerative
conditions while maintaining homeostasis. Our work identifies PGDHi as a
translatable intervention to rejuvenate aged HSCs and mitigate hematopoietic
decline.
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