1. Developmental Biology

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

  1. Yun Deng
  2. Haihong Wang
  3. Xiaohui Liu
  4. Hao Yuan
  5. Jin Xu
  6. Hugues de Thé
  7. Jun Zhou  Is a corresponding author
  8. Jun Zhu  Is a corresponding author
  1. Shanghai Jiao Tong University, China
  2. South China University of Technology, China
  3. Inserm, France
https://doi.org/10.7554/eLife.80760
Share this article
Cite this article
  1. Yun Deng
  2. Haihong Wang
  3. Xiaohui Liu
  4. Hao Yuan
  5. Jin Xu
  6. Hugues de Thé
  7. Jun Zhou
  8. Jun Zhu
(2022)
Zbtb14 regulates monocyte and macrophage development through inhibiting pu.1 expression in zebrafish
eLife 11:e80760.
https://doi.org/10.7554/eLife.80760
  2. Download BibTeX
  3. Download .RIS

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

  1. Yun Deng

    Shanghai Institute of Hematology, Shanghai Jiao Tong University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.

  2. Haihong Wang

    Shanghai Institute of Hematology, Shanghai Jiao Tong University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.

  3. Xiaohui Liu

    Shanghai Institute of Hematology, Shanghai Jiao Tong University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.

  4. Hao Yuan

    Shanghai Institute of Hematology, Shanghai Jiao Tong University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.

  5. 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.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6840-1359

  6. Hugues de Thé

    UMR 1050, Inserm, Paris, France
    Competing interests
    The authors declare that no competing interests exist.

  7. 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.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0472-3188

  8. 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.
    ORCID icon "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

© 2022, Deng et al.

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.

Metrics

  • 1,022
    views
  • 220
    downloads
  • 8
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Yun Deng
  2. Haihong Wang
  3. Xiaohui Liu
  4. Hao Yuan
  5. Jin Xu
  6. Hugues de Thé
  7. Jun Zhou
  8. Jun Zhu
(2022)
Zbtb14 regulates monocyte and macrophage development through inhibiting pu.1 expression in zebrafish
eLife 11:e80760.
https://doi.org/10.7554/eLife.80760

Share this article

https://doi.org/10.7554/eLife.80760

Categories and tags

Research organism

Further reading

    1. Developmental Biology

    Tgfbr1 regulates lateral plate mesoderm and endoderm reorganization during the trunk to tail transition

    Anastasiia Lozovska, Ana Casaca ... Moises Mallo
    Research Article

    During the trunk to tail transition the mammalian embryo builds the outlets for the intestinal and urogenital tracts, lays down the primordia for the hindlimb and external genitalia, and switches from the epiblast/primitive streak (PS) to the tail bud as the driver of axial extension. Genetic and molecular data indicate that Tgfbr1 is a key regulator of the trunk to tail transition. Tgfbr1 has been shown to control the switch of the neuromesodermal competent cells from the epiblast to the chordoneural hinge to generate the tail bud. We now show that in mouse embryos Tgfbr1 signaling also controls the remodeling of the lateral plate mesoderm (LPM) and of the embryonic endoderm associated with the trunk to tail transition. In the absence of Tgfbr1, the two LPM layers do not converge at the end of the trunk, extending instead as separate layers until the caudal embryonic extremity, and failing to activate markers of primordia for the hindlimb and external genitalia. The vascular remodeling involving the dorsal aorta and the umbilical artery leading to the connection between embryonic and extraembryonic circulation was also affected in the Tgfbr1 mutant embryos. Similar alterations in the LPM and vascular system were also observed in Isl1 null mutants, indicating that this factor acts in the regulatory cascade downstream of Tgfbr1 in LPM-derived tissues. In addition, in the absence of Tgfbr1 the embryonic endoderm fails to expand to form the endodermal cloaca and to extend posteriorly to generate the tail gut. We present evidence suggesting that the remodeling activity of Tgfbr1 in the LPM and endoderm results from the control of the posterior PS fate after its regression during the trunk to tail transition. Our data, together with previously reported observations, place Tgfbr1 at the top of the regulatory processes controlling the trunk to tail transition.

    1. Developmental Biology
    2. Neuroscience

    Aberrant FGF signaling promotes granule neuron precursor expansion in SHH subgroup infantile medulloblastoma

    Odessa R Yabut, Jessica Arela ... Samuel J Pleasure
    Research Article

    Mutations in Sonic Hedgehog (SHH) signaling pathway genes, for example, Suppressor of Fused (SUFU), drive granule neuron precursors (GNP) to form medulloblastomas (MBSHH). However, how different molecular lesions in the Shh pathway drive transformation is frequently unclear, and SUFU mutations in the cerebellum seem distinct. In this study, we show that fibroblast growth factor 5 (FGF5) signaling is integral for many infantile MBSHH cases and that FGF5 expression is uniquely upregulated in infantile MBSHH tumors. Similarly, mice lacking SUFU (Sufu-cKO) ectopically express Fgf5 specifically along the secondary fissure where GNPs harbor preneoplastic lesions and show that FGFR signaling is also ectopically activated in this region. Treatment with an FGFR antagonist rescues the severe GNP hyperplasia and restores cerebellar architecture. Thus, direct inhibition of FGF signaling may be a promising and novel therapeutic candidate for infantile MBSHH.

    1. Developmental Biology
    2. Genetics and Genomics

    Evaluating the transcriptional regulators of arterial gene expression via a catalogue of characterized arterial enhancers

    Svanhild Nornes, Susann Bruche ... Sarah De Val
    Research Article

    The establishment and growth of the arterial endothelium requires the coordinated expression of numerous genes. However, regulation of this process is not yet fully understood. Here, we combined in silico analysis with transgenic mice and zebrafish models to characterize arterial-specific enhancers associated with eight key arterial identity genes (Acvrl1/Alk1, Cxcr4, Cxcl12, Efnb2, Gja4/Cx37, Gja5/Cx40, Nrp1 and Unc5b). Next, to elucidate the regulatory pathways upstream of arterial gene transcription, we investigated the transcription factors binding each arterial enhancer compared to a similar assessment of non-arterial endothelial enhancers. These results found that binding of SOXF and ETS factors was a common occurrence at both arterial and pan-endothelial enhancers, suggesting neither are sufficient to direct arterial specificity. Conversely, FOX motifs independent of ETS motifs were over-represented at arterial enhancers. Further, MEF2 and RBPJ binding was enriched but not ubiquitous at arterial enhancers, potentially linked to specific patterns of behaviour within the arterial endothelium. Lastly, there was no shared or arterial-specific signature for WNT-associated TCF/LEF, TGFβ/BMP-associated SMAD1/5 and SMAD2/3, shear stress-associated KLF4 or venous-enriched NR2F2. This cohort of well characterized and in vivo-verified enhancers can now provide a platform for future studies into the interaction of different transcriptional and signalling pathways with arterial gene expression.