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

Vivian Y. Chang; Yuwei He; Samantha Grohe; Morgan R. Brady; Aldi Chan; Rucha S. Kadam; Tiancheng Fang; Amara Pang; Katherine Pohl; Evelyn Tran; Michelle Li; Jenny Kan; Yurun Zhang; Josie J. Lu; Joshua P. Sasine; Heather A. Himburg; Peibin Yue; John P. Chute

iScience (Jul 2024)

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

Vivian Y. Chang,
Yuwei He,
Samantha Grohe,
Morgan R. Brady,
Aldi Chan,
Rucha S. Kadam,
Tiancheng Fang,
Amara Pang,
Katherine Pohl,
Evelyn Tran,
Michelle Li,
Jenny Kan,
Yurun Zhang,
Josie J. Lu,
Joshua P. Sasine,
Heather A. Himburg,
Peibin Yue,
John P. Chute

Affiliations

Vivian Y. Chang: Division of Hematology-Oncology, Department of Pediatrics, UCLA, Los Angeles, CA, USA; Children’s Discovery and Innovation Institute, UCLA, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA, USA
Yuwei He: Division of Hematology & Cellular Therapy, Cedars Sinai Medical Center, Los Angeles, CA, USA
Samantha Grohe: Division of Hematology & Cellular Therapy, Cedars Sinai Medical Center, Los Angeles, CA, USA
Morgan R. Brady: Division of Hematology & Cellular Therapy, Cedars Sinai Medical Center, Los Angeles, CA, USA
Aldi Chan: Division of Hematology & Cellular Therapy, Cedars Sinai Medical Center, Los Angeles, CA, USA
Rucha S. Kadam: Division of Hematology & Cellular Therapy, Cedars Sinai Medical Center, Los Angeles, CA, USA
Tiancheng Fang: Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, CA, USA
Amara Pang: Division of Hematology/Oncology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
Katherine Pohl: Division of Hematology/Oncology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
Evelyn Tran: Division of Hematology/Oncology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
Michelle Li: Division of Hematology/Oncology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
Jenny Kan: Division of Hematology/Oncology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
Yurun Zhang: Molecular Biology Institute, UCLA, Los Angeles, CA 90095, USA
Josie J. Lu: Applied Genomics, Computation and Translational Core, Cedars Sinai Medical Center, Los Angeles, CA, USA
Joshua P. Sasine: Division of Hematology & Cellular Therapy, Cedars Sinai Medical Center, Los Angeles, CA, USA
Heather A. Himburg: Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, USA
Peibin Yue: Division of Hematology & Cellular Therapy, Cedars Sinai Medical Center, Los Angeles, CA, USA
John P. Chute: Division of Hematology & Cellular Therapy, Cedars Sinai Medical Center, Los Angeles, CA, USA; Board of Governors Regenerative Medicine Institute, Cedars Sinai Medical Center, Los Angeles, CA 90095, USA; Samuel Oschin Cancer Center, Cedars Sinai Medical Center, Los Angeles, CA 90095, USA; Department of Medicine, Cedars Sinai Medical Center, Los Angeles, CA 91361, USA; Corresponding author

Journal volume & issue: Vol. 27, no. 7
p. 110306

Abstract

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Summary: 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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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