Histone deacetylase 1 and 2 drive differentiation and fusion of progenitor cells in human placental trophoblasts
CELL DEATH & DISEASE
Authors: Bhattad, Gargi Jaju; Jeyarajah, Mariyan J.; McGill, Megan G.; Dumeaux, Vanessa; Okae, Hiroaki; Arima, Takahiro; Lajoie, Patrick; Berube, Nathalie G.; Renaud, Stephen J.
Abstract
Cell fusion occurs when several cells combine to form a multinuclear aggregate (syncytium). In human placenta, a syncytialized trophoblast (syncytiotrophoblast) layer forms the primary interface between maternal and fetal tissue, facilitates nutrient and gas exchange, and produces hormones vital for pregnancy. Syncytiotrophoblast development occurs by differentiation of underlying progenitor cells called cytotrophoblasts, which then fuse into the syncytiotrophoblast layer. Differentiation is associated with chromatin remodeling and specific changes in gene expression mediated, at least in part, by histone acetylation. However, the epigenetic regulation of human cytotrophoblast differentiation and fusion is poorly understood. In this study, we found that human syncytiotrophoblast development was associated with deacetylation of multiple core histone residues. Chromatin immunoprecipitation sequencing revealed chromosomal regions that exhibit dynamic alterations in histone H3 acetylation during differentiation. These include regions containing genes classically associated with cytotrophoblast differentiation (TEAD4, TP63, OVOL1, CGB), as well as near genes with novel regulatory roles in trophoblast development and function, such as LHX4 and SYDE1. Prevention of histone deacetylation using both pharmacological and genetic approaches inhibited trophoblast fusion, supporting a critical role of this process for trophoblast differentiation. Finally, we identified the histone deacetylases (HDACs) HDAC1 and HDAC2 as the critical mediators driving cytotrophoblast differentiation. Collectively, these findings provide novel insights into the epigenetic mechanisms underlying trophoblast fusion during human placental development.
Isolates of Cryptococcus neoformans serotype A and D developed on canavanine-glycine-bromthymol blue medium
MYCOSES
Authors: Nakamura, Y; Kano, R; Sato, H; Watanabe, S; Takahashi, H; Hasegawa, A
Abstract
Two isolates of Cryptococcus neoformans serotype A and one isolate of serotype D from pigeon droppings were found to grow on canavanine-glycine-bromthymol blue (CGB) medium, when the Japanese isolates of Cr. neoformans were examined for their serotype and biochemical characteristics. The susceptibility to canavanine and the activity in assimilation of glycine were analysed on these three isolates. They were resistant to canavanine at the high concentration of 3.6 mmoll(-1) and developed by assimilating the glycine even at a concentration of 7 mmoll(-1). These isolates were proved to develop well on CGB medium, which contains 0.1 mmoll(-1) of canavanine and 133 mmoll(-1) of glycine. Three isolates of Cr. neoformans developed on CGB medium were also confirmed to be serotype A or D by the molecular analysis.