TBX3 reciprocally controls key trophoblast lineage decisions in villi during human placenta development in the first trimester

作者全名："Yi, Cen; Song, Honglan; Liang, Hongxiu; Ran, Yujie; Tang, Jing; Chen, Enxiang; Li, Fangfang; Chen, Fengming; Fu, Lijuan; Wang, Yingxiong; Ding, Yubin; Xie, Youlong"

作者地址："[Yi, Cen; Song, Honglan; Wang, Yingxiong; Ding, Yubin; Xie, Youlong] Chongqing Med Univ, Women & Childrens Hosp, Dept Obstet & Gynecol, Chongqing, Peoples R China; [Yi, Cen; Song, Honglan; Liang, Hongxiu; Ran, Yujie; Tang, Jing; Chen, Enxiang; Li, Fangfang; Wang, Yingxiong; Ding, Yubin; Xie, Youlong] Chongqing Med Univ, Sch Publ Hlth, Joint Int Res Lab Reprod & Dev, Minist Educ China, Chongqing 400016, Peoples R China; [Fu, Lijuan] Chongqing Hosp Tradit Chinese Med, Dept Gynecol, Chongqing 400021, Peoples R China; [Fu, Lijuan] Chongqing Med Univ, Sch Tradit Chinese Med, Chongqing Key Lab Tradit Chinese Med Prevent & Cur, Chongqing 400016, Peoples R China; [Fu, Lijuan] Changsha Med Univ, Dept Basic Med Sci, Changsha 410219, Hunan, Peoples R China; [Chen, Fengming] Changsha Med Univ, Hunan Prov Key Lab Tradit Chinese Med Agr Biogenom, Changsha 410219, Peoples R China"

通信作者："Xie, YL (通讯作者)，Chongqing Med Univ, Women & Childrens Hosp, Dept Obstet & Gynecol, Chongqing, Peoples R China.; Xie, YL (通讯作者)，Chongqing Med Univ, Sch Publ Hlth, Joint Int Res Lab Reprod & Dev, Minist Educ China, Chongqing 400016, Peoples R China."

来源：INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001198944700001

JCR分区：Q1

影响因子：8.2

年份：2024

卷号：263

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Placenta; Trophoblast lineage decisions; TBX3; MAPK; FAK

摘要："Human trophoblastic lineage development is intertwined with placental development and pregnancy outcomes, but the regulatory mechanisms underpinning this process remain inadequately understood. In this study, based on single-nuclei RNA sequencing (snRNA-seq) analysis of the human early maternal-fetal interface, we compared the gene expression pattern of trophoblast at different developmental stages. Our findings reveal a predominant upregulation of TBX3 during the transition from villous cytotrophoblast (VCT) to syncytiotrophoblast (SCT), but downregulation of TBX3 as VCT progresses into extravillous trophoblast cells (EVT). Immunofluorescence analysis verified the primary expression of TBX3 in SCT, partial expression in MKi67-positive VCT, and absence in HLA-G-positive EVT, consistent with our snRNA-seq results. Using immortalized trophoblastic cell lines (BeWo and HTR8/SVneo) and human primary trophoblast stem cells (hTSCs), we observed that TBX3 knockdown impedes SCT formation through RAS-MAPK signaling, while TBX3 overexpression disrupts the cytoskeleton structure of EVT and hinders EVT differentiation by suppressing FAK signaling. In conclusion, our study suggests that the spatiotemporal expression of TBX3 plays a critical role in regulating trophoblastic lineage development via distinct signaling pathways. This underscores TBX3 as a key determinant during hemochorial placental development."

基金机构："National Natural Science Foundation of China [82101767, 82171664, 82101762, 82301909]; Natural Science Foundation of Chongqing Municipality of China [CSTB2022NSsdot;CQ-LZX0062]; Chongqing Postdoctoral Science Foundation [cstc2021jcyj-bshX0105]"

基金资助正文："Funding This work was supported by the National Natural Science Foundation of China [grant numbers 82101767, 82171664, 82101762, 82301909] and the Natural Science Foundation of Chongqing Municipality of China [grant numbers CSTB2022NS & sdot;CQ-LZX0062] , Chongqing Postdoctoral Science Foundation [grant numbers cstc2021jcyj-bshX0105] ."