Myc Promotes Polyploidy in Murine Trophoblast Cells and Suppresses Senescence

Overview

Journal Development

Specialty Biology

Date 2023 Jun 6

PMID 37278344

Authors

Vijay Pratap Singh

Huzaifa Hassan

Fengyan Deng

Dai Tsuchiya

Sean McKinney

Kevin Ferro

Jennifer L Gerton

Affiliations

Soon will be listed here.

Abstract

The placenta is essential for reproductive success. The murine placenta includes polyploid giant cells that are crucial for its function. Polyploidy occurs broadly in nature but its regulators and significance in the placenta are unknown. We have discovered that many murine placental cell types are polyploid and have identified factors that license polyploidy using single-cell RNA sequencing. Myc is a key regulator of polyploidy and placental development, and is required for multiple rounds of DNA replication, likely via endocycles, in trophoblast giant cells. Furthermore, MYC supports the expression of DNA replication and nucleotide biosynthesis genes along with ribosomal RNA. Increased DNA damage and senescence occur in trophoblast giant cells without Myc, accompanied by senescence in the neighboring maternal decidua. These data reveal Myc is essential for polyploidy to support normal placental development, thereby preventing premature senescence. Our study, combined with available literature, suggests that Myc is an evolutionarily conserved regulator of polyploidy.

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