is Essential for the Quiescence and Maintenance of Adult Hematopoietic Stem Cells Under Stress

Overview

Journal iScience

Publisher Cell Press

Date 2021 Feb 3

PMID 33532716

Citations 4

Authors

Zhigang Li

Xuemei Fu

Weiru Wu

Zhilong Liu

Zhe Chen

Chengfang Zhou

Yuanyuan Liu

Mei Kuang

Fangfang Sun

Feifei Xiao

Yongxiu Huang

Xiaojun Zhang

Shijun Fan

Xingqin Huang

Guangling Zheng

Jieping Chen

Yu Hou

Affiliations

Soon will be listed here.

Abstract

Zinc finger protein 521 (), a quiescent hematopoietic stem cell (HSC)-enriched transcription factor, is involved in the self-renewal and differentiation of fetal liver HSC. However, its role in adult hematopoiesis remains elusive. Here, we found that deletion did not inhibit adult hematopoiesis under homeostatic conditions. In contrast, -null chimeric mice showed significantly reduced pool size of HSC and hematopoietic progenitor cells associated with increased apoptosis and loss of quiescence. Competitive serial transplantation assays revealed that regulates HSC self-renewal and differentiation under regenerative stress. Mechanistically, transcriptionally repressed expression by increasing H3K9ac and decreasing H3K9me3 levels in its promoter. Knockdown of inhibited the hyper-activated NF-κB pathway and reversed the loss of quiescence in -null HSC under stress. Thus, our results reveal a previously unrecognized role for as critical regulator of quiescence and self-renewal of HSC in adult hematopoiesis mediated at least partly by controlling expression.

Citing Articles

Exploring the contribution of Zfp521/ZNF521 on primary hematopoietic stem/progenitor cells and leukemia progression.

Chiarella E Cell Tissue Res. 2024; 398(3):161-173.

PMID: 39436449 PMC: 11614986. DOI: 10.1007/s00441-024-03926-2.

ZNF521 promotes acute myeloid leukemogenesis by suppressing the expression and acetylation of SMC3.

Qin R, Yang T, Jiang H, Yu M Heliyon. 2024; 10(18):e37528.

PMID: 39309877 PMC: 11415694. DOI: 10.1016/j.heliyon.2024.e37528.

Cell-intrinsic factors governing quiescence vis-à-vis activation of adult hematopoietic stem cells.

Budgude P, Vaidya A, Kale V Mol Cell Biochem. 2022; 478(6):1361-1382.

PMID: 36309884 DOI: 10.1007/s11010-022-04594-y.

Enhanced ZNF521 expression induces an aggressive phenotype in human ovarian carcinoma cell lines.

Scicchitano S, Montalcini Y, Lucchino V, Melocchi V, Gigantino V, Chiarella E PLoS One. 2022; 17(10):e0274785.

PMID: 36191006 PMC: 9529122. DOI: 10.1371/journal.pone.0274785.

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