Centrosome Clustering in the Development of Bovine Binucleate Trophoblast Giant Cells

Abstract

Binucleate trophoblast giant cells (BNC) are the characteristic feature of the ruminant placenta. During their development, BNC pass through 2 acytokinetic mitoses and become binucleate with 2 tetraploid nuclei. In this study, we investigate the number and location of centrosomes in bovine BNC. Centrosomes typically consist of 2 centrioles surrounded by electron-dense pericentriolar material. Duplication of centrosomes is tightly linked to the cell cycle, which ensures that the number of centrosomes remains constant in proliferating diploid cells. Alterations of the cell cycle, which affect the number of chromosome sets, also affect the number of centrosomes. In this study, we use placentomal tissue from pregnant cows (gestational days 80-230) for immunohistochemical staining of γ-tubulin (n = 3) and transmission electron microscopy (n = 3). We show that mature BNC have 4 centrosomes with 8 centrioles, clustered in the angle between the 2 cell nuclei. During the second acytokinetic mitosis, the centrosomes must be clustered to form the poles of a bipolar spindle. In rare cases, centrosome clustering fails and tripolar mitosis leads to the formation of trinucleate “BNC”. Generally, centrosome clustering occurs in polyploid tumor cells, which have an increased number of centrioles, but it is absent in proliferating diploid cells. Thus, inhibition of centrosome clustering in tumor cells is a novel promising strategy for cancer treatment. BNC are a cell population in which centrosome clustering occurs as part of the normal life history. Thus, they might be a good model for the study of the molecular mechanisms of centrosome clustering.

Polyploid giant cancer cells: Unrecognized actuators of tumorigenesis, metastasis, and resistance

“…There is a small body of literature specifically related to PGCCs (74 PubMed‐listed entries with query: [PGCCs] vs 3,857,567 with query [cancer]; accessed 10 May 2019; Figure ), but this literature, taken holistically, makes a compelling case for defining them as the essential keystone cancer species and actuators of tumorigenesis, therapeutic resistance, and recurrence in metastatic disease. Keystone species are relatively few in number, but have a significant impact on the health and composition of the ecosystem.…”

Loss of ninein interferes with osteoclast formation and causes premature ossification

“…Furthermore, a truncation mutation in cNap1 in cows is at the origin of centriole splitting and cell migration defects, as well as Seckel-like syndromes ( Floriot et al, 2015 ). Clustering of centrioles may also contribute to the functionality of placental cells and thereby insure early embryonic growth, since specialized cells of the embryonic trophoectoderm, trophoblast giant cells, are polyploid and display centrosome amplification ( Klisch et al, 2017 ; Buss et al, 2022 ), with clustered centrioles identified in binucleate bovine trophoblast cells ( Klisch et al, 2017 ). Thus, early embryonic growth defects in our ninein-deficient mouse embryos may be explained in part by impaired centriole clustering, in addition to potential abnormalities in proliferation and cell death.…”

Postmitotic centriole disengagement and maturation leads to centrosome amplification in polyploid trophoblast giant cells

“…These represent different paths towards polyploidy, including endocycling, cell fusion and cell division failure. (Klisch et al, 2017;Sakaue-Sawano et al, 2013;Simmons et al, 2007;Simmons & Cross, 2005;Zybina & Zybina, 2005;Zybina & Zybina, 1996).…”

“…These represent different paths toward polyploidy, including endocycling, cell fusion, and cell division failure ( Zybina and Zybina, 1996 , 2005 ; Simmons and Cross, 2005 ; Simmons et al ., 2007 ; Sakaue-Sawano et al. , 2013 ; Klisch et al. , 2017 ).…”