Zbtb14 regulates monocyte and macrophage development through inhibiting pu.1 expression in zebrafish

Abstract
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Abstract

Macrophages and their precursor cells, monocytes, are the first line of defense of the body against foreign pathogens and tissue damage. Although the origins of macrophages are diverse, some common transcription factors (such as PU.1) are required to ensure proper development of monocytes/macrophages. Here we report that the deficiency of zbtb14, a transcription repressor gene belonging to ZBTB family, leads to an aberrant expansion of monocyte/macrophage population in zebrafish. Mechanistically, Zbtb14 functions as a negative regulator of pu.1, and SUMOylation on a conserved lysine is essential for the repression activity of Zbtb14. Moreover, a serine to phenylalanine mutation found in an acute myeloid leukemia (AML) patient could target ZBTB14 protein to autophagic degradation. Hence, ZBTB14 is a newly identified gene implicated in both normal and malignant myelopoiesis.

Data availability

RNA sequencing dataset generated in this study was deposited with Dryad-https://doi.org/10.5061/dryad.9cnp5hqms.

The following data sets were generated

1. Deng Y
2. Wang H
3. Liu X
4. Yuan H
5. Xu J
6. de Thé H
7. Zhou J
8. Zhu J
(2022) RNA SEQ
Dryad Digital Repository, doi:10.5061/dryad.9cnp5hqms.

https://dx.doi.org/10.5061/dryad.9cnp5hqms

Article and author information

Author details

Yun Deng

Shanghai Institute of Hematology, Shanghai Jiao Tong University, Shanghai, China

Competing interests
The authors declare that no competing interests exist.
Haihong Wang

Shanghai Institute of Hematology, Shanghai Jiao Tong University, Shanghai, China

Competing interests
The authors declare that no competing interests exist.
Xiaohui Liu

Shanghai Institute of Hematology, Shanghai Jiao Tong University, Shanghai, China

Competing interests
The authors declare that no competing interests exist.
Hao Yuan

Shanghai Institute of Hematology, Shanghai Jiao Tong University, Shanghai, China

Competing interests
The authors declare that no competing interests exist.
Jin Xu

Division of Cell, Developmental and Integrative Biology, South China University of Technology, Guangzhou, China

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-6840-1359
Hugues de Thé

UMR 1050, Inserm, Paris, France

Competing interests
The authors declare that no competing interests exist.
Jun Zhou

Shanghai Institute of Hematology, Shanghai Jiao Tong University, Shanghai, China

For correspondence
zj10802@rjh.com.cn

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-0472-3188
Jun Zhu

CNRS-LIA Hematology and Cancer, Shanghai Jiao Tong University, Shanghai, China

For correspondence
zhuj1966@yahoo.com

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-7983-3130

Funding

National Natural Science Foundation of China (NO.32171097)

Jun Zhou

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Ethics StatementThe study was approved by the Ethics Committee of Rui Jin Hospital Affiliated toShanghai Jiao Tong University School of Medicine. Zebrafish experimental procedures were conducted in accordance with the protocols approved by the Institutional Animal Care and Use Committee (IACUC) of Shanghai Jiao Tong University (2020-3#).

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.