Chromatin accessibility analysis reveals regulatory dynamics of developing human retina and hiPSC-derived retinal organoids
SCIENCE ADVANCES
Authors: Xie, Haohuan; Zhang, Wen; Zhang, Mei; Akhtar, Tasneem; Li, Young; Yi, Wenyang; Sun, Xiao; Zuo, Zuqi; Wei, Min; Fang, Xin; Yao, Ziqin; Dong, Kai; Zhong, Suijuan; Liu, Qiang; Shen, Yong; Wu, Qian; Wang, Xiaoqun; Zhao, Huan; Bao, Jin; Qu, Kun; Xue, Tian
Abstract
Retinal organoids (ROs) derived from human induced pluripotent stem cells (hiPSCs) provide potential opportunities for studying human retinal development and disorders; however, to what extent ROs recapitulate the epigenetic features of human retinal development is unknown. In this study, we systematically profiled chromatin accessibility and transcriptional dynamics over long-term human retinal and RO development. Our results showed that ROs recapitulated the human retinogenesis to a great extent, but divergent chromatin features were also discovered. We further reconstructed the transcriptional regulatory network governing human and RO retinogenesis in vivo. Notably, NFIB and THRA were identified as regulators in human retinal development. The chromatin modifications between developing human and mouse retina were also cross-analyzed. Notably, we revealed an enriched bivalent modification of H3K4me3 and H3K27me3 in human but not in murine retinogenesis, suggesting a more dedicated epigenetic regulation on human genome.
Polychlorinated Biphenyl-Related Alterations of the Expression of Essential Genes in Harbour Seals (Phoca vitulina) from Coastal Sites in Canada and the United States
ARCHIVES OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY
Authors: Noel, Marie; Dangerfield, Neil; Jeffries, Steve; Lambourn, Dyanna; Lance, Monique; Helbing, Caren; Lebeuf, Michel; Ross, Peter S.
Abstract
As long-lived marine mammals found throughout the temperate coastal waters of the North Pacific and Atlantic Oceans, harbour seals (Phoca vitulina) have become an invaluable sentinel of food-web contamination. Their relatively high trophic position predisposes harbour seals to the accumulation of harmful levels of persistent organic pollutants (POPs). We obtained skin/blubber biopsy samples from live-captured young harbour seals from various sites in the northeastern Pacific (British Columbia, Canada, and Washington State, USA) as well as the northwestern Atlantic (Newfoundland and Quebec, Canada). We developed harbour seal-specific primers to investigate the potential impact of POP exposure on the expression of eight important genes. We found correlations between the blubber mRNA levels of three of our eight target genes and the dominant persistent organic pollutant in seals [polychlorinated biphenyls (PCBs)] including estrogen receptor alpha (Esr1: r(2) = 0.12, p = 0.038), thyroid hormone receptor alpha (Thra: r(2) = 0.16; p = 0.028), and glucocorticoid receptor (Nr3c1: r(2) = 0.12; p = 0.049). Age, sex, weight, and length were not confounding factors on the expression of genes. Although the population-level consequences are unclear, our results suggest that PCBs are associated with alterations of the expression of genes responsible for aspects of metabolism, growth and development, and immune function. Collectively, these results provide additional support for the use of harbour seals as indicators of coastal food-web contamination.