2. Academic Validation
  3. Epidermal growth factor augments the self-renewal capacity of aged hematopoietic stem cells

Epidermal growth factor augments the self-renewal capacity of aged hematopoietic stem cells

  • iScience. 2024 Jun 19;27(7):110306. doi: 10.1016/j.isci.2024.110306.
Vivian Y Chang 1 2 3,  Yuwei He 4,  Samantha Grohe 4,  Morgan R Brady 4,  Aldi Chan 4,  Rucha S Kadam 4,  Tiancheng Fang 5,  Amara Pang 6,  Katherine Pohl 6,  Evelyn Tran 6,  Michelle Li 6,  Jenny Kan 6,  Yurun Zhang 7,  Josie J Lu 8,  Joshua P Sasine 4,  Heather A Himburg 9,  Peibin Yue 4,  John P Chute 4 10 11 12
Affiliations

Affiliations

  • 1 Division of Hematology-Oncology, Department of Pediatrics, UCLA, Los Angeles, CA, USA.
  • 2 Children's Discovery and Innovation Institute, UCLA, Los Angeles, CA, USA.
  • 3 Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA, USA.
  • 4 Division of Hematology & Cellular Therapy, Cedars Sinai Medical Center, Los Angeles, CA, USA.
  • 5 Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, CA, USA.
  • 6 Division of Hematology/Oncology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
  • 7 Molecular Biology Institute, UCLA, Los Angeles, CA 90095, USA.
  • 8 Applied Genomics, Computation and Translational Core, Cedars Sinai Medical Center, Los Angeles, CA, USA.
  • 9 Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, USA.
  • 10 Board of Governors Regenerative Medicine Institute, Cedars Sinai Medical Center, Los Angeles, CA 90095, USA.
  • 11 Samuel Oschin Cancer Center, Cedars Sinai Medical Center, Los Angeles, CA 90095, USA.
  • 12 Department of Medicine, Cedars Sinai Medical Center, Los Angeles, CA 91361, USA.
PMID: 39055915 DOI: 10.1016/j.isci.2024.110306
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.

Keywords

Human physiology; cellular physiology; functional aspects of cell biology; molecular medicine; stem cells research.

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