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Lead exposure reduces survival, neuronal determination, and differentiation of P19 stem cells.
Neurotoxicology and Teratology ( IF 2.9 ) Pub Date : 2019-02-15 , DOI: 10.1016/j.ntt.2019.01.005
Clayton Mansel 1 , Shaneann Fross 1 , Jesse Rose 1 , Emily Dema 1 , Alexis Mann 1 , Haley Hart 1 , Paul Klawinski 1 , Bhupinder P S Vohra 1
Affiliation  

Lead (Pb) is a teratogen that poses health risks after acute and chronic exposure. Lead is deposited in the bones of adults and is continuously leached into the blood for decades. While this chronic lead exposure can have detrimental effects on adults such as high blood pressure and kidney damage, developing fetuses and young children are particularly vulnerable. During pregnancy, bone-deposited lead is released into the blood at increased rates and can cross the placental barrier, exposing the embryo to the toxin. Embryos exposed to lead display serious developmental and cognitive defects throughout life. Although studies have investigated lead's effect on late-stage embryos, few studies have examined how lead affects stem cell determination and differentiation. For example, it is unknown whether lead is more detrimental to neuronal determination or differentiation of stem cells. We sought to determine the effect of lead on the determination and differentiation of pluripotent embryonic testicular carcinoma (P19) cells into neurons. Our data indicate that lead exposure significantly inhibits the determination of P19 cells to the neuronal lineage by alteration of N-cadherin and Sox2 expression. We also observed that lead significantly alters subsequent neuronal and glial differentiation. Consequently, this research emphasizes the need to reduce public exposure to lead.

中文翻译:

铅暴露降低了P19干细胞的存活率,神经元测定和分化。

铅(Pb)是一种致畸物,在急性和慢性暴露后会造成健康危险。铅沉积在成年人的骨骼中,数十年来不断浸入血液中。尽管这种长期的铅暴露会对成年人产生有害影响,例如高血压和肾脏损害,但发育中的胎儿和幼儿尤其脆弱。在怀孕期间,骨沉积的铅以增加的速率释放到血液中,并且可以穿过胎盘屏障,使胚胎暴露于毒素。暴露于铅的胚胎在整个生命中都表现出严重的发育和认知缺陷。尽管研究调查了铅对晚期胚胎的影响,但很少有研究检查铅如何影响干细胞的确定和分化。例如,目前尚不清楚铅是否对神经元的测定或干细胞的分化有害。我们试图确定铅对多能胚胎睾丸癌(P19)细胞向神经元的分化和分化的影响。我们的数据表明,铅暴露通过改变N-钙黏着蛋白和Sox2表达,显着抑制P19细胞对神经元谱系的测定。我们还观察到铅显着改变了随后的神经元和神经胶质分化。因此,这项研究强调必须减少公众对铅的接触。我们的数据表明,铅暴露通过改变N-钙黏着蛋白和Sox2表达,显着抑制P19细胞对神经元谱系的测定。我们还观察到铅显着改变了随后的神经元和神经胶质分化。因此,这项研究强调必须减少公众对铅的接触。我们的数据表明,铅暴露通过改变N-钙黏着蛋白和Sox2表达,显着抑制了P19细胞对神经元谱系的测定。我们还观察到铅显着改变了随后的神经元和神经胶质分化。因此,这项研究强调必须减少公众对铅的接触。
更新日期:2019-11-01
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