The aryl hydrocarbon receptor directs the differentiation of murine progenitor blastomeres.
The aryl hydrocarbon receptor directs the differentiation of murine progenitor blastomeres.
复制标题
DOI：
10.1007/s10565-022-09755-9
复制
发表时间：
2023-08
影响因子：
6.1
通讯作者：
中科院分区：
文献类型：
--
作者：
哺乳动物胚胎发生过程中卵裂分裂的关键调控决定着着床前胚胎细胞的命运。对早期2-细胞、4-细胞和8-细胞卵裂球的单细胞RNA测序表明，传统上被认为是环境感受器的芳烃受体(AHR)指导着卵裂球的分化。在AhR基因敲除的胚胎或暴露于二恶英的母鼠胚胎中，AHR功能的破坏显著地损害了囊胚的形成，导致OCT4和CDX2转录异质性的抑制和丧失，以及多能性的非特异性下调。轨迹--分化途径--和基因变异性分析进一步证实，OCT4功能的解除调控和AHR功能中断导致的转录异质性的变化限制了4-细胞胚胎中分化卵裂球的出现。AHR似乎指导着前体卵裂球的分化，植入前AHR功能的中断可能会显著扰乱胚胎发育，导致子代成年后长期处于疾病核心的状态。网上版载有补充材料，可在10.1007/s10565.022-09755-9查阅。
Key regulatory decisions during cleavage divisions in mammalian embryogenesis determine the fate of preimplantation embryonic cells. Single-cell RNA sequencing of early-stage—2-cell, 4-cell, and 8-cell—blastomeres show that the aryl hydrocarbon receptor (AHR), traditionally considered as an environmental sensor, directs blastomere differentiation. Disruption of AHR functions in Ahr knockout embryos or in embryos from dams exposed to dioxin, the prototypic xenobiotic AHR agonist, significantly impairs blastocyst formation, causing repression and loss of transcriptional heterogeneity of OCT4 and CDX2 and incidence of nonspecific downregulation of pluripotency. Trajectory—the path of differentiation—and gene variability analyses further confirm that deregulation of OCT4 functions and changes of transcriptional heterogeneity resulting from disruption of AHR functions restrict the emergence of differentiating blastomeres in 4-cell embryos. It appears that AHR directs the differentiation of progenitor blastomeres and that disruption of preimplantation AHR functions may significantly perturb embryogenesis leading to long-lasting conditions at the heart of disease in offspring’s adulthood. The online version contains supplementary material available at 10.1007/s10565-022-09755-9.
登录
查看更多内容
影响因子：
64.5
作者：
Goolam M;Scialdone A;Graham SJL;Macaulay IC;Jedrusik A;Hupalowska A;Voet T;Marioni JC;Zernicka-Goetz M
通讯作者：
Zernicka-Goetz M
影响因子：
1.2
作者：
Ko, Chia-I;Wang, Qin;Fan, Yunxia;Xia, Ying;Puga, Alvaro
通讯作者：
Puga, Alvaro
DOI：
10.1073/pnas.190256997
发表时间：
2000-09-12
影响因子：
11.1
作者：
Lahvis, GP;Lindell, SL;Bradfield, CA
通讯作者：
Bradfield, CA
DOI：
10.1007/978-3-319-62414-3_5
发表时间：
2017-01-01
期刊：
PERICONCEPTION IN PHYSIOLOGY AND MEDICINE
影响因子：
--
作者：
Fleming, Tom P.;Eckert, Judith J.;Denisenko, Oleg
通讯作者：
Denisenko, Oleg
影响因子：
16
作者：
Jung, Yoon Hee;Kremsky, Isaac;Corces, Victor G.
通讯作者：
Corces, Victor G.