RUNX3 levels in human hematopoietic progenitors are regulated by aging and dictate erythroid-myeloid balance

被引：14

作者：

Balogh, Peter ^{[1
]}

Adelman, Emmalee R. ^{[2
]}

Pluvinage, John, V ^{[3
]}

Capaldo, Brian J. ^{[4
]}

Freeman, Katie C. ^{[1
]}

Singh, Sandeep ^{[1
]}

Elagib, Kamaleldin E. ^{[1
]}

Nakamura, Yukio ^{[5
]}

Kurita, Ryo ^{[6
]}

Sashida, Goro ^{[7
]}

Zunder, Eli R. ^{[8
]}

Li, Hui ^{[1
]}

Gru, Alejandro A. ^{[1
]}

Price, Elizabeth A. ^{[9
]}

Schrier, Stanley L. ^{[9
]}

Weissman, Irving L. ^{[10
]}

Figueroa, Maria E. ^{[2
]}

Pang, Wendy W. ^{[11
]}

Goldfarb, Adam N. ^{[1
]}

机构：

[1] Univ Virginia, Sch Med, Dept Pathol, Charlottesville, VA 22908 USA

[2] Univ Miami Hlth Syst, Sylvester Comprehens Canc Ctr, Miami, FL USA

[3] Stanford Univ, Dept Med, Stanford, CA 94305 USA

[4] Univ Virginia, Sch Med, Flow Cytometry Core Facil, Charlottesville, VA 22908 USA

[5] RIKEN BioResource Ctr, Cell Engn Div, Tsukuba, Ibaraki, Japan

[6] Japanese Red Cross Soc, Res & Dev Dept, Blood Serv Headquarters, Cent Blood Inst,Koto Ku, Tokyo, Japan

[7] Kumamoto Univ, Lab Transcript Regulat Leukemogenesis IRCMS, Chuo Ku, Kumamoto, Japan

[8] Univ Virginia, Dept Biomed Engn, Charlottesville, VA USA

[9] Stanford Univ, Dept Med, Div Hematol, Stanford, CA 94305 USA

[10] Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA

[11] Stanford Univ, Dept Med, Div Blood & Bone Marrow Transplantat, Stanford, CA 94305 USA

来源：

HAEMATOLOGICA | 2020年 / 105卷 / 04期

关键词：

TUMOR-SUPPRESSOR; TRANSCRIPTION FACTORS; CELL; METHYLATION; GENES; PROLIFERATION; REVEALS; YOUNG; AGE;

D O I：

10.3324/haematol.2018.208918

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Healthy bone marrow progenitors yield a co-ordinated 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 hematopoietic stem and progenitor cell aging, and a key determinant of erythroid-myeloid lineage balance.

引用

页码：905 / 913

页数：9

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