A transcriptome comparison of time‐matched developing human, mouse and rat neural progenitor cells reveals human uniqueness
A transcriptome comparison of time‐matched developing human, mouse and rat neural progenitor cells reveals human uniqueness
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时间匹配的发育中的人类、小鼠和大鼠神经祖细胞的转录组比较揭示了人类的独特性
DOI：
10.1016/j.taap.2018.05.009
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发表时间：
2018
影响因子：
3.8
通讯作者：
E. Fritsche
中科院分区：
文献类型：
--
作者：
S. Masjosthusmann;D. Becker;B. Petzuch;J. Klose;Clara Siebert;R. Deenen;M. Barenys;J. Baumann;Katharina Dach;J. Tigges;Ulrike Hübenthal;K. Köhrer;E. Fritsche
人们普遍认为，人类大脑发育具有啮齿动物无法代表的独特特征。明显的原因是进化上的距离和生理上的差异。当啮齿动物被用于安全性或药理疗效研究时，这可能会导致错误的预测。为了更好地将以动物为基础的研究转化为人类情况，人体体外系统可能是有用的。在这项研究中，我们通过分析神经分化过程中神经前体细胞转录组的变化来表征发育中的神经前体细胞。此外，我们还确定了调节神经发育过程(如迁移和分化)的中枢分子。其中三个枢纽的调节对这些过程的影响是在特定物种的背景下研究的。我们发现，尽管这三个物种的基因表达谱在质量和数量上存在很大差异，但它们在细胞迁移、胶质发生、神经发生或多细胞生物体的发育等方面存在相似的GO术语。识别的HUB分子的药理调节触发了物种特异性的细胞反应。这项研究强调了在分子水平上了解物种差异的重要性，并倡导使用基于人类的体外模型进行药理学和毒理学研究。
It is widely accepted that human brain development has unique features that cannot be represented by rodents. Obvious reasons are the evolutionary distance and divergent physiology. This might lead to false predictions when rodents are used for safety or pharmacological efficacy studies. For a better translation of animal-based research to the human situation, human in vitro systems might be useful. In this study, we characterize developing neural progenitor cells from prenatal human and time-matched rat and mouse brains by analyzing the changes in their transcriptome profile during neural differentiation. Moreover, we identify hub molecules that regulate neurodevelopmental processes like migration and differentiation. Consequences of modulation of three of those hubs on these processes were studied in a species-specific context. We found that although the gene expression profiles of the three species largely differ qualitatively and quantitatively, they cluster in similar GO terms like cell migration, gliogenesis, neurogenesis or development of multicellular organism. Pharmacological modulation of the identified hub molecules triggered species-specific cellular responses. This study underlines the importance of understanding species differences on the molecular level and advocates the use of human based in vitro models for pharmacological and toxicological research.
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DOI：
10.14573/altex.1406111
发表时间：
2014
期刊：
ALTEX
影响因子：
--
作者：
Alépée N;Bahinski A;Daneshian M;De Wever B;Fritsche E;Goldberg A;Hansmann J;Hartung T;Haycock J;Hogberg H;Hoelting L;Kelm JM;Kadereit S;McVey E;Landsiedel R;Leist M;Lübberstedt M;Noor F;Pellevoisin C;Petersohn D;Pfannenbecker U;Reisinger K;Ramirez T;Rothen-Rutishauser B;Schäfer-Korting M;Zeilinger K;Zurich MG
通讯作者：
Zurich MG
DOI：
--
发表时间：
1997-11
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Monique Bos;John Mendelsohn;Young Mee Kim;Joan Albanell;David W. Fry;David W. Fry;José Baselga
通讯作者：
Monique Bos;John Mendelsohn;Young Mee Kim;Joan Albanell;David W. Fry;David W. Fry;José Baselga
影响因子：
6.1
作者：
Krug, Anne K.;Kolde, Raivo;Gaspar, John A.;Rempel, Eugen;Balmer, Nina V.;Meganathan, Kesavan;Vojnits, Kinga;Baquie, Mathurin;Waldmann, Tanja;Ensenat-Waser, Roberto;Jagtap, Smita;Evans, Richard M.;Julien, Stephanie;Peterson, Hedi;Zagoura, Dimitra;Kadereit, Suzanne;Gerhard, Daniel;Sotiriadou, Isaia;Heke, Michael;Natarajan, Karthick;Henry, Margit;Winkler, Johannes;Marchan, Rosemarie;Stoppini, Luc;Bosgra, Sieto;Westerhout, Joost;Verwei, Miriam;Vilo, Jaak;Kortenkamp, Andreas;Hescheler, Jurgen;Hothorn, Ludwig;Bremer, Susanne;van Thriel, Christoph;Krause, Karl-Heinz;Hengstler, Jan G.;Rahnenfuehrer, Jorg;Leist, Marcel;Sachinidis, Agapios
通讯作者：
Sachinidis, Agapios
影响因子：
13.8
作者：
A. Strasser;Hans-Joachim Wittmann;A. Buschauer;E. Schneider;R. Seifert
通讯作者：
A. Strasser;Hans-Joachim Wittmann;A. Buschauer;E. Schneider;R. Seifert