Effects of per- and poly-fluorinated alkyl substances on pancreatic and endocrine differentiation of human pluripotent stem cells

CORC > 生态环境研究中心 > 中国科学院生态环境研究中心 > 环境化学与生态毒理学国家重点实验室

	Effects of per- and poly-fluorinated alkyl substances on pancreatic and endocrine differentiation of human pluripotent stem cells
	Liu, Shuyu; Yang, Renjun; Yin, Nuoya; Faiola, Francesco
刊名	CHEMOSPHERE
	2020-09
卷号	254 页码:1-12
关键词	Per- and poly-fluorinated alkyl substances (PFASs) PFOS/PFOA Human pluripotent stem cells Pancreatic and endocrine progenitors Developmental toxicity
ISSN号	0045-6535
英文摘要	Perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) are typical per- and polyfluorinated alkyl substances (PFASs) that epidemiological studies have already associated with diabetes. However, insufficient data on their toxicity have been reported to explain any mechanism of action, which could justify such an association. Meanwhile, short-chain PFASs designed to substitute PFOA and PFOS, have already raised increasing concerns for their biosafety. Here, we evaluated whether common PFASs affected pancreatic and endocrine cell development using a human pluripotent stem cell pancreatic induction model and human pancreatic progenitor cell (hPP) endocrine induction model. The short-chain PFASs, pentafluorobenzoic acid, perfluorohexanoic acid, perfluorobutanesulfonic acid, and perfluorohexanesulfonic acid, homologous to PFOA or PFOS, did not significantly disrupt hPP generation, unlike PFOA and PFOS, based on pancreatic and duodenal homeobox 1 (PDX1) expression. However, SRY box 9 (SOX9) expression was suppressed in PDX1+ hPPs. All six PFASs did not disrupt SOX9 expression or hPP proliferation. However, endocrine differentiation of hPPs was affected, as indicated by neurogenin-3 (NGN3) downregulation, owing to abnormal increases in SOX9 and hairy and enhancer of split-1 (HES1) expressions. Thus, hyperactivation of NOTCH signaling was repressed after hPPs committed to the endocrine lineage. In conclusion, our study demonstrates how powerful human pluripotent stem cell-based pancreatic differentiation models can be in developmental toxicity evaluations, compared to traditional toxicity assays, mostly based on live animals. Moreover, our findings suggest that PFASs may alter pancreatic development after the pancreatic domain emerges from the gut tube, and provide in- sights into their toxicity mechanisms. (C) 2020 Elsevier Ltd. All rights reserved.
内容类型	期刊论文
源URL	[http://ir.rcees.ac.cn/handle/311016/44667]
专题	生态环境研究中心_环境化学与生态毒理学国家重点实验室
推荐引用方式 GB/T 7714	Liu, Shuyu,Yang, Renjun,Yin, Nuoya,et al. Effects of per- and poly-fluorinated alkyl substances on pancreatic and endocrine differentiation of human pluripotent stem cells[J]. CHEMOSPHERE,2020,254:1-12.
APA	Liu, Shuyu,Yang, Renjun,Yin, Nuoya,&Faiola, Francesco.(2020).Effects of per- and poly-fluorinated alkyl substances on pancreatic and endocrine differentiation of human pluripotent stem cells.CHEMOSPHERE,254,1-12.
MLA	Liu, Shuyu,et al."Effects of per- and poly-fluorinated alkyl substances on pancreatic and endocrine differentiation of human pluripotent stem cells".CHEMOSPHERE 254(2020):1-12.