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Epidermal growth factor augments the self-renewal capacity of aged hematopoietic stem cells.
Chang, Vivian Y; He, Yuwei; Grohe, Samantha; Brady, Morgan R; Chan, Aldi; Kadam, Rucha S; Fang, Tiancheng; Pang, Amara; Pohl, Katherine; Tran, Evelyn; Li, Michelle; Kan, Jenny; Zhang, Yurun; Lu, Josie J; Sasine, Joshua P; Himburg, Heather A; Yue, Peibin; Chute, John P.
Afiliação
  • Chang VY; Division of Hematology-Oncology, Department of Pediatrics, UCLA, Los Angeles, CA, USA.
  • He Y; Children's Discovery and Innovation Institute, UCLA, Los Angeles, CA, USA.
  • Grohe S; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA, USA.
  • Brady MR; Division of Hematology & Cellular Therapy, Cedars Sinai Medical Center, Los Angeles, CA, USA.
  • Chan A; Division of Hematology & Cellular Therapy, Cedars Sinai Medical Center, Los Angeles, CA, USA.
  • Kadam RS; Division of Hematology & Cellular Therapy, Cedars Sinai Medical Center, Los Angeles, CA, USA.
  • Fang T; Division of Hematology & Cellular Therapy, Cedars Sinai Medical Center, Los Angeles, CA, USA.
  • Pang A; Division of Hematology & Cellular Therapy, Cedars Sinai Medical Center, Los Angeles, CA, USA.
  • Pohl K; Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, CA, USA.
  • Tran E; Division of Hematology/Oncology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
  • Li M; Division of Hematology/Oncology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
  • Kan J; Division of Hematology/Oncology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
  • Zhang Y; Division of Hematology/Oncology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
  • Lu JJ; Division of Hematology/Oncology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
  • Sasine JP; Molecular Biology Institute, UCLA, Los Angeles, CA 90095, USA.
  • Himburg HA; Applied Genomics, Computation and Translational Core, Cedars Sinai Medical Center, Los Angeles, CA, USA.
  • Yue P; Division of Hematology & Cellular Therapy, Cedars Sinai Medical Center, Los Angeles, CA, USA.
  • Chute JP; Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, USA.
iScience ; 27(7): 110306, 2024 Jul 19.
Article em En | MEDLINE | ID: mdl-39055915
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: IScience Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: IScience Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos