SETD7 promotes lateral plate mesoderm formation by modulating the Wnt/β-catenin signaling pathway

Ding Wang; Yapu Li; Changlu Xu; Hongtao Wang; Xin Huang; Xu Jin; Sirui Ren; Jie Gao; Jingyuan Tong; Jinhua Liu; Jiaxi Zhou; Lihong Shi

doi:10.1016/j.isci.2023.106917

SETD7 promotes lateral plate mesoderm formation by modulating the Wnt/β-catenin signaling pathway

iScience. 2023 May 19;26(6):106917. doi: 10.1016/j.isci.2023.106917. eCollection 2023 Jun 16.

Authors

Ding Wang^{1

2}, Yapu Li^{1

2}, Changlu Xu^{1

2}, Hongtao Wang^{1

2}, Xin Huang^{1

2}, Xu Jin^{1

2}, Sirui Ren^{1

2}, Jie Gao^{1

2}, Jingyuan Tong^{1

2}, Jinhua Liu^{1

2}, Jiaxi Zhou^{1

2}, Lihong Shi^{1

3

2}

Affiliations

¹ State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
² CAMS Center for Stem Cell Medicine, PUMC Department of Stem Cell and Regenerative Medicine, Tianjin 300020, China.
³ Tianjin Institutes of Health Science, Tianjin 301600, China.

Abstract

The role of SET domain containing 7 (SETD7) during human hematopoietic development remains elusive. Here, we found that deletion of SETD7 attenuated the generation of hematopoietic progenitor cells (HPCs) during the induction of hematopoietic differentiation from human embryonic stem cells (hESCs). Further analysis specified that SETD7 was required for lateral plate mesoderm (LPM) specification but dispensable for the generation of endothelial progenitor cells (EPCs) and HPCs. Mechanistically, rather than depending on its histone methyltransferase activity, SETD7 interacted with β-catenin at lysine residue 180 facilitated its degradation. Diminished SETD7 expression led to the accumulation of β-catenin and the consequent activation of the Wnt signaling pathway, which altered LPM patterning and facilitated the production of paraxial mesoderm (PM). Taken together, the findings indicate that SETD7 is related to LPM and PM patterning via posttranslational regulation of the Wnt/β-catenin signaling pathway, providing novel insights into mesoderm specification during hematopoietic differentiation from hESCs.

Keywords: Biological sciences; Developmental biology; Embryology; Molecular biology.