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RUNX3 levels in human hematopoietic progenitors are regulated by aging and dictate erythroid-myeloid balance. Haematologica Balogh, P. n., Adelman, E. R., Pluvinage, J. V., Capaldo, B. J., Freeman, K. C., Singh, S. n., Elagib, K. E., Nakamura, Y. n., Kurita, R. n., Sashida, G. n., Zunder, E. R., Li, H. n., Gru, A. A., Price, E. A., Schrier, S. L., Weissman, I. L., Figueroa, M. E., Pang, W. W., Goldfarb, A. N. 2019

Abstract

Healthy bone marrow progenitors yield a coordinated balance of hematopoietic lineages. This balance shifts with aging toward enhanced granulopoiesis with diminished erythropoiesis and lymphopoiesis, changes which likely contribute to the development of bone marrow disorders in the elderly. In this study, RUNX3 was identified as a hematopoietic stem and progenitor cell factor whose levels decline with aging in humans and mice. This decline is exaggerated in hematopoietic stem and progenitor cells from subjects diagnosed with unexplained anemia of the elderly. Hematopoietic stem cells from elderly unexplained anemia patients had diminished erythroid but unaffected granulocytic colony forming potential. Knockdown studies revealed human hematopoietic stem and progenitor cells to be strongly influenced by RUNX3 levels, with modest deficiencies abrogating erythroid differentiation at multiple steps while retaining capacity for granulopoiesis. Transcriptome profiling indicated control by RUNX3 of key erythroid transcription factors, including KLF1 and GATA1. These findings thus implicate RUNX3 as a participant in HSPC aging, and a key determinant of erythroid-myeloid lineage balance.

View details for DOI 10.3324/haematol.2018.208918

View details for PubMedID 31171641