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Epidermal growth factor augments the self-renewal capacity of aged hematopoietic stem cells. iScience 2024 Jul 19;27(7):110306

Date

07/26/2024

Pubmed ID

39055915

Pubmed Central ID

PMC11269946

DOI

10.1016/j.isci.2024.110306

Scopus ID

2-s2.0-85197589903 (requires institutional sign-in at Scopus site)

Abstract

Hematopoietic aging is associated with decreased hematopoietic stem cell (HSC) self-renewal capacity and myeloid skewing. We report that culture of bone marrow (BM) HSCs from aged mice with epidermal growth factor (EGF) suppressed myeloid skewing, increased multipotent colony formation, and increased HSC repopulation in primary and secondary transplantation assays. Mice transplanted with aged, EGF-treated HSCs displayed increased donor cell engraftment within BM HSCs and systemic administration of EGF to aged mice increased HSC self-renewal capacity in primary and secondary transplantation assays. Expression of a dominant negative EGFR in Scl/Tal1+ hematopoietic cells caused increased myeloid skewing and depletion of long term-HSCs in 15-month-old mice. EGF treatment decreased DNA damage in aged HSCs and shifted the transcriptome of aged HSCs from genes regulating cell death to genes involved in HSC self-renewal and DNA repair but had no effect on HSC senescence. These data suggest that EGFR signaling regulates the repopulating capacity of aged HSCs.

Author List

Chang VY, He Y, Grohe S, Brady MR, Chan A, Kadam RS, Fang T, Pang A, Pohl K, Tran E, Li M, Kan J, Zhang Y, Lu JJ, Sasine JP, Himburg HA, Yue P, Chute JP

Author

Heather A. Himburg PhD Associate Professor in the Radiation Oncology department at Medical College of Wisconsin