E-mail: wangyl@ioz.ac.cn
Address: Jia 3 Datun Road, Chaoyang District, Beijing
Postcode: 100101
Research Areas
The mammalian pregnancy beginning from the recognition and adhesion of trophoblast cells of blastocyst with endometrium, and further invasion into the latter. The formation of the placenta is one of the critical events in mammalian pregnancy. Owing to the appropriately controlled invasion to uterine stroma and spiral arteries remodeling by placental trophoblasts, the utero-placental circulation can be successfully formed. Failures in the regulatory network of trophoblast functions will lead to serious clinical complications, such as preeclampsia, recurrent miscarriage, and fetal growth restriction, etc. These disorders bring severe burden for maternal and perinatal care, even cause health problems for the affected mothers and children in their short-term and long-term development.
So far, the understanding of human placenta is still a "black box", the regulatory mechanisms underlying placental development and the maternal adaptation to pregnancy remain largely unknown. The prediction, prevention, and treatment of the placenta-associated pregnant diseases are also urgently needed.
Under the guidance of cutting-edge scientific issues and major national needs, Wang Lab is committed to studying the regulation mechanism of placental development and pregnancy maintenance, as well as the pathogenesis of major pregnancy diseases such as gestational hypertension and recurrent spontaneous abortion. It aims to demystify human pregnancy health and lay a solid scientific foundation for the development of prediction and intervention strategies for pregnancy diseases.
Wang Lab has established and maintained several in vitro models, including the culture system for human trophoblast cells differentiating to different pathways, three-dimensional co-culture system of trophoblasts-endothelial cells, trophoblast stem cells, and decidual NK cells, etc. We have successfully established several placenta specific gene manipulation mouse models using strategies of CYP19-Cre, ELF5-Cre or lentivirus/adenovirus-mediated gene delivery. We have discovered that placental trophoblast syncytialization potentiates macropinocytosis via mTOR signaling to adapt to reduced amino acid supply, explained that protein O-GlcNAcylation modification fine-tunes trophoblast cells syncytialization, revealed the immune modulating function of endovascular extravillous trophoblasts (enEVTs) and the fate of vascular smooth muscle cells dedifferentiation in the process of uterine spiral arteries remodeling, systematically elucidated the cellular and molecular regulatory networks of pregnancy adaptation at the maternal-fetal interface. A prospective resource bank of pregnant diseases has been established through collaborating with multi-center clinical units. A batch of molecular markers for early diagnosis of preeclampsia were obtained. The mechanism of dysregulated multicellular interaction and the molecular pathway of maternal pregnancy adaptation at the maternal-fetal interface involved in the occurrence and development of preeclampsia, FGR, recurrent spontaneous abortion, etc were revealed. Nearly 100 research papers have been published in peer-reviewed journals including Cell Stem Cell, PNAS, Hypertension, etc.
Generally, the research in Dr. Wang’s lab is aiming to understand the regulatory mechanisms of placenta development in human beings, and to deepen the understanding on the pathogenesis of severe pregnancy-associated diseases including preeclampsia (PE), recurrent spontaneous abortion (RSA) and fetal growth restriction (FGR). The long-term goal is to reveal the critical checkpoint in placenta development that governs pregnancy outcomes, and to figure out reliable and specific molecular targets for early diagnosis and intervention of the relevant diseases.
Specific research aims include: 1. The lineage programming of the placental trophoblast cells. 2. Mechanisms underlying the establishment of uterine-placental-fetal circulation. 3. The cellular and molecular basis of the immune adaptation during pregnancy. 4. The etiology of severe pregnant diseases such as preeclampsia and recurrent miscarriage.
Education
Dr. Wang received her B.A. in Biology (1993) from University of Science and Technology in China, and Ph.D. in Reproductive Physiology (1998) from the State Key Laboratory of Stem Cells and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences. She was appointed Professor in 2004 in the Institute of Zoology.
Honors & Distinctions
Publications
Papers
(2) Xu P#, Ma Y#, Wu H and Wang YL*. Placenta-Derived MicroRNAs in the Pathophysiology of Human Pregnancy., Front Cell Dev Biol., 2021, corresponding author
(3) Liu J#, Shao X#, Qin W#, Yu X, Dang F, Yang Q, Li YX, Chen X, Wang C*, Wang YL*. Quantitative chemoproteomics reveals O-GlcNAcylation of Cystathionine γ-lyase (CSE) represses trophoblast syncytialization., Cell Chem Biol., 2021, corresponding author
(4) Yang Q#, Ma Y#, Liu Y, Shao X, Jia W, Yu X, Li YX, Yang L, Gu W, Wang H, Wang J*, Wang YL*. MNSFβ regulates placental development by conjugating IGF2BP2 to enhance trophoblast cell invasiveness, Cell Prolif, 2021, corresponding author
(5) Ma Y#, Yu X#, Li YX, Wang YL*. HGF/ c-Met signal regulates early differentiation of placental trophoblast cells, J Reprod Dev, 2021, corresponding author
(6) Zhen XX#, Yang L#, Gu Y, Yang Q, Gu WW, He YP, Wang YL*, Wang J*. MNSFbeta Regulates TNFalpha Production by Interacting with RC3H1 in Human Macrophages, and Dysfunction of MNSFbeta in Decidual Macrophages Is Associated With Recurrent Pregnancy Loss, Front Immunol, 2021, corresponding author
(7) Bian X, Liu J, Yang Q, Liu Y, Jia W, Zhang X, Li YX, Shao X*, Wang YL*. miR-210 regulates placental adaptation to maternal hypoxic stress during pregnancy., Biol Reprod, 2021, corresponding author
(8) Shao X#, Cao G#, Chen D#, Liu J, Yu B, Liu M, Li YX, Cao B*, Sadovsky Y*, Wang YL*. Placental trophoblast syncytialization potentiates macropinocytosis via mTOR signaling to adapt to reduced amino acid supply., PNAS, 2021, corresponding author
(9) Ma Y#, Yu X#, Zhang L#, Liu J, Shao X, Li YX, Wang YL*. Uterine decidual niche modulates the progressive dedifferentiation of spiral artery vascular smooth muscle cells during human pregnancy., Biol Reprod., 2021, corresponding author
(10) Ma Y#, Yang Q#, Fan M#, Zhang L, Gu Y, Jia W, Li Z, Wang F, Li YX, Wang J, Li R*, Shao X*, Wang YL*. Placental endovascular extravillous trophoblasts (enEVTs) educate maternal T-cell differentiation along the maternal-placental circulation., Cell Proliferation., 2020, corresponding author
(11) Li Z#, Bian X#, Ma Y, Yang Q, Jia W, Liu J, Wang F, Liu M, Li YX, Shao X*, Wang YL*.Uterine Scarring Leads to Adverse Pregnant Consequences by Impairing the Endometrium Response to Steroids., Endocrinology, 2020, corresponding author
(12) Wang H#, Zhao Y#, Luo R, Bian X, Wang Y, Shao X, Li YX, Liu M*, Wang YL*. A positive feedback self-regulatory loop between miR-210 and HIF-1αmediated by CPEB2 is involved in trophoblast syncytialization: implication of trophoblast malfunction in preeclampsia., Biol Reprod., 2020, corresponding author
(13) Xu P#, Li Z#, Wang Y#, Yu X, Shao X, Li YX, Peng C, Zhao Y*, Wang YL*. miR-18a Contributes to Preeclampsia by Downregulating Smad2 (Full Length) and Reducing TGF-β Signaling., Mol Ther Nucleic Acids., 2020, corresponding author
(14) Xu P#, Li Z#, Wang Y#, Yu X, Shao X, Li YX, Peng C, Zhao Y*, Wang YL*. MiR-18a contributes to pre 1 eclampsia by downregulating Smad2 (full-length) and reducing transforming growth factor-β signaling., Molecular Therapy - Nucleic Acids., 2020, corresponding author
(15) Xuan Shao, Yongqing Wang, Yanlei Liu, Xuejiang Guo, Dong Li, Ran Huo, Wentong Jia, Guangming Cao, Yu-Xia Li, Ming Liu, Jiahao Sha, Yangyu Zhao, and Yan-Ling Wang. Association of imbalanced sex hormone production with excessive procoagulation factor SerpinF2 in preeclampsia., Journal of Hypertension, 2019, corresponding author
(16) Lin L, Li G, Zhang W, Wang Y* and Yang H*. Low-dose aspirin reduces hypoxia-induced sFlt1 release via the JNK/AP-1 pathway in human trophoblast and endothelial cells., Journal of Cellular Physiology, 2019, corresponding author
(17) Hao Wang, Yangyu Zhao, Rongcan Luo, Xiaotao Bian, Yongqing Wang, Xuan Shao, Yu-xia Li, Ming Liu, Yan-Ling Wang. A positive feedback self-regulatory loop between miR-210 and HIF-1α mediated by CPEB2 is involved in trophoblast syncytiolization: implication of trophoblast malfunction in preeclampsia Self-regulatory loop for trophoblast malfunction., Biology of Reproduction, 2019, corresponding author
(18) Shao X#, Tan C, Chen D, Wang YL*. Placental defects are involved in most gene mutations that cause embryonic and fetal death. Biol Reprod. 2018 Sep 1;99(3):476-478, Biol Reprod, 2018, corresponding author
(19) Dai J#, Liang K, Zhao S, Jia W, Liu Y, Wu H, Lv J, Cao C, Chen T, Zhuang S, Hou X, Zhou S, Zhang X, Chen XW, Huang Y, Xiao RP, Wang YL, Luo T, Xiao J, Wang C*. Chemoproteomics reveals baicalin activates hepatic CPT1 to ameliorate diet-induced obesity and hepatic steatosis. Proc Natl Acad Sci U S A. 2018 Jun 11. pii: 201801745., Proc Natl Acad Sci U S A, 2018,
(20) Li G#, Ma L, Lin L, Wang YL, Yang H*. The intervention effect of aspirin on a lipopolysaccharide-induced preeclampsia-like mouse model by inhibiting the NF-κB pathway. Biol Reprod. 2018 Aug 1;99(2):422-432., Biol Reprod, 2018,
(21) Wang H#, Zhang L, Guo X, Bai Y, Li YX, Sha J, Peng C, Wang YL*, Liu M. MiR-195 modulates oxidative stress-induced apoptosis and mitochondrial energy production in human trophoblasts via flavin adenine dinucleotide-dependent oxidoreductase domain-containing protein 1 and pyruvate dehydrogenase phosphatase regulatory subunit. J Hypertens. 2018 Feb;36(2):306-318., J Hypertens, 2018, corresponding author
(22) Shao X, Wang Y, Liu Y, Guo X, Li D, Huo R, Jia W, Cao G, Li YX, Liu M, Sha J, Zhao Y, Wang YL*. Association of imbalanced sex hormone production with excessive procoagulation factor SerpinF2 in preeclampsia. 2018 Jul 16. doi: 10.1097/HJH.0000000000001862. [Epub ahead of print], J Hypertension, 2018, corresponding author
(23) Liu M#, Wang Y#, Lu H#, Wang H, Shi X, Shao X, Li YX, Zhao Y*, Wang YL*. miR-518b Enhances Human Trophoblast Cell Proliferation Through Targeting Rap1b and Activating Ras-MAPK Signal. Front Endocrinol (Lausanne). 2018 15(9):100, Front Endocrinol (Lausanne), 2018, corresponding author
(24) Ma L#, Li G#, Cao G#, Zhu Y, Du MR, Zhao Y, Wang H, Liu Y, Yang Y, Li YX, Li DJ, Yang H, Wang YL*. dNK cells facilitate the interaction between trophoblastic and endothelial cells via VEGF-C and HGF. Immunol Cell Biol. 2017, 95(8):695-704, Immunol Cell Biol, 2017, corresponding author
(25) Shao X#, Liu Y#, Liu M, Wang Y, Yan L, Wang H, Ma L, Lia YX, Zhao Y*, Wang YL*. Testosterone represses estrogen signaling via upregulating mir-22: mechanism for imbalanced steroid hormone production in preeclampsia. Hypertension, 2017, 69:721-730 (Editorial highlight), Hypertension, 2017, corresponding author
(26) Liu M, Cao G, Zhang Y, Qu J, Li W, Wan X, Li YX, Zhang Z, Wang YL, Gao F. Changes in the morphology and protein expression of germ cells and Sertoli cells in plateau pikas testes during non-breeding season. Sci Rep. 2016 Mar 4;6:22697., Scientific Reports, 2016, corresponding author
(27) Wu H#, Wang H#, Liu M, Bai Y, Li YX, Ji L, Peng C, Yu Y*, Wang YL*. MiR-195 participates in the placental disorder of preeclampsia via targeting activin receptor type-2B in trophoblastic cells. J Hypertens. 2016,34(7):1371-9, J Hypertens, 2016, corresponding author
(28) Luo R#, Wang Y#, Xu P#, Cao G, Zhao Y, Shao X, Li YX, Chang C, Peng C, Wang YL*. Hypoxia-inducible miR-210 contributes to preeclampsia via targeting thrombospondin type I domain containing 7A. Sci Rep, 2016, 6:19588., Scientific Reports, 2016, corresponding author
(29) Optimising Sample Collection for Placental Research, PLACENTA, 2014,
(30) MicroRNA-210 contributes to preeclampsia by down-regulating KCMF1, Hypertension, 2014, corresponding author
(31) Variations of MicroRNAs in Human Placentas and Plasma From Preeclamptic Pregnancy, HYPERTENSION, 2014, corresponding author
(32) Maturation of GDF15 in human placental trophoblast cells depends on the interaction with matrix metalloproteinase-26 (MMP-26)., J Clin Endo Metab, 2014, corresponding author
(33) Placental Trophoblast Cell Differentiation:Physiological Regulation and Pathological Relevance to Preeclampsia, MOLECULAR ASPECTS OF MEDICINE, 2013,
(34) The imprinted H19 gene regulates human placental trophoblast cell proliferation via encoding miR-675 that targets Nodal Modulator 1 (NOMO1), RNA BIOLOGY, 2012, corresponding author
(35) Downregulated miR-195 Detected in Preeclamptic Placenta Affects Trophoblast Cell Invasion via Modulating ActRIIA Expression, PLOS ONE, 2012,
(36) Self-Control of HGF Regulation on Human Trophoblast Cell Invasion via Enhancing c-Met Receptor Shedding by ADAM10 and ADAM17, JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2012, corresponding author
(37) High Levels of Activin A Detected in Preeclamptic Placenta Induce Trophoblast Cell Apoptosis by Promoting Nodal Signaling, JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2012, corresponding author
(38) Detection of global DNA methylation and paternally imprinted H19 gene methylation in preeclamptic placentas, HYPERTENSION RESEARCH, 2011,
(39) GnRH I and II up-regulate MMP-26 expression through the JNK pathway in human cytotrophoblasts, Reproductive Biology and Endocrinology : RB&E, 2010,
(40) Prostasin Regulates Human Placental Trophoblast Cell Proliferation via the EGFR Signaling Pathway., Human Reproduction, 2010, corresponding author
(41) Study on the correlation between soluble Met and preeclampsia, 2009,
(42) Promotion of Human Trophoblasts Invasion by Gonadotropin-Releasing Hormone (GnRH) I and GnRH II via Distinct Signaling Pathways, MOLECULAR ENDOCRINOLOGY, 2009, corresponding author
(43) Prostasin inhibits cell invasion in human choriocarcinomal JEG-3 cells, HISTOCHEMISTRY AND CELL BIOLOGY, 2009, corresponding author
(44) Hormonal and Paracrine Regulation of Embryonic Implantation: A Workshop Report, PLACENTA, 2007,
(45) An immortalized normal human cytotrophoblast cell line generated by exogenous expression of telomeric reverse transcriptase., 2006, first author
(46) Dual effect of TGFβ1 on cell adhesion and invasion in human normal placenta trophoblast cells., 2006, corresponding author
(47) Spatio-temporal expression of matrix metalloproteinase-26 in human placental trophoblasts and fetal red cells during normal placentation, BIOLOGY OF REPRODUCTION, 2005,
(48) Dynamic expression of matrix metalloproteinases (MMP-2,-9 and-14) and the tissue inhibitors of MMPs (TIMP-1,-2 and-3) at the implantation site during tubal pregnancy, REPRODUCTION, 2005,
(49) Differential regulation of ERa and ERb in primate mammary gland., 2005, first author
(50) Determination of genes involved in the early process of embryonic implantation in rhesus monkey (Macaca mulatta) by suppression subtractive hybridization, BIOLOGY OF REPRODUCTION, 2004,
(51) Temporal and spatial expression of integrins and their extracellular matrix ligands at the maternal-fetal interface in the rhesus monkey during pregnancy, BIOLOGY OF REPRODUCTION, 2003,
Grants
l National Key Research and Development Program (Grant No. 2021YFC2700303): Abnormal cell linage development, embryo suspension and early abortion (P.I., 2021.12-2024.11). Amount: RMB 3,000,000
l National Key Research and Development Program (Grant No. 2018YFC1004100): Molecular mechanisms of placenta formation (P.I. 2018.12-2021.12). Amount: RMB 2,540,000/27,300,000
l National Natural Science Foundation of China Key Research Project (Grant No. 81730040): The mechanism of steroid hormone synthesis and metabolism disturbance during pregnancy leading to the development of preeclampsia (P.I. 2018.01-2022.12). Amount: RMB 2,940,000
l National Key Research and Development Program (Grant No. 2016YFC1000200): Basic research on establishment and application of assisted Reproductive population and progeny cohort in Chinese population (P.I. 2016.07-2021.06). Amount: RMB 2,650,000
l National Natural Science Foundation Research Project (Grant No. 31571191): Regulation of maternal coagulation-fibrinolysis balance and pregnancy outcomes by placenta-derived steroid hormones (P.I., 2016.01-2019.12). Amount: RMB 750,000
l National Natural Science Foundation Major Research Project (Grant No. 81490740): Pathological mechanisms of recurrent spontaneous abortion and preeclampsia caused by abnormal feto-maternal interactions (P.I., 2015.01-2019.12). Amount: RMB 1,800,000
l NSFC-CIHR joint project (Grant No. 81361128008): MicroRNAs as biomarkers and therapeutic targets of preeclampsia (P.I., 2014.01-2016.12). Amount: RMB 1,000,000
l The National Natural Science Foundation for Distinguished Young Scholars (Grant No. 81025004): Placenta development and the pathogenesis of preeclampsia (P.I., 2011.01-2014.12). Amount: RMB 2,000,000
l The knowledge Innovation Program in CAS (Grant No. KSCX2-EW-R-06): Study on the biomarkers and diagnosis strategy for preeclampsia and other pregnancy-associated diseases (P.I., 2011.01-2013.12). Amount: RMB 960,000
l The Special Funds for Major State Basic Research Project (Grant No. 2011CB944404): Molecular basis for pregnancy establishment and maintenance (Major participant, 2011.01-2014.12). Amount: RMB 1,500,000
l NSFC-CIHR joint project (Grant No. 30811120430): Role of microRNAs in preeclampsia (P.I., 2009.01-2011.12). Amount: RMB 450,000
Students
Graduated students
Xin Zeng Ph.D. 071003-Physiology
Xiaojie Ma Ph.D. 071003-Physiology
Wenlong Gao Ph.D. 071008-Developmental Biology
Dong Li Ph.D. 071008-Developmental Biology
Bin Cao Ph.D. 071008-Developmental Biology
Ling Yu Ph.D. 071008-Developmental Biology
Weiwei Yang Ph.D. 071008-Developmental Biology
Yanyan Yang Ph.D. 071008-Developmental Biology
Yang Bai Ph.D. 071008-Developmental Biology
Xuan Shao Ph.D. 071008-Developmental Biology
Peng Xu Ph.D. 071008-Developmental Biology
Sisi Li Ph.D. 071008-Developmental Biology
Liyang Ma MSc 071008-Developmental Biology
Guanlin Li Ph.D. 071008-Developmental Biology
Guangming Cao Ph.D. 071008-Developmental Biology
Huifen Lu Ph.D. 100104-Pathology and Pathophysiology
Hao Wang Ph.D. 071008-Developmental Biology
Yamei Jiang MSc 071008-Developmental Biology
Liyang Ma Ph.D. 071008-Developmental Biology
Yanlei Liu Ph.D. 100104-Pathology and Pathophysiology
Xiaotao Bian Ph.D. 100104-Pathology and Pathophysiology
Wentong Jia Ph.D. 100104-Pathology and Pathophysiology
Feihong Dang MSc 100104-Pathology and Pathophysiology
Zhilang Li Ph.D. 100104-Pathology and Pathophysiology
Haili Bao Ph.D. 071008-Developmental Biology
Juan Liu Ph.D. 100104-Pathology and Pathophysiology
Yeling Ma Ph.D. 100104-Pathology and Pathophysiology
Feiyang Wang Ph.D. 100104-Pathology and Pathophysiology
Ungraduated students
Xin Yu Ph.D. 100104-Pathology and Pathophysiology
Qianqian Li MSc 100104-Pathology and Pathophysiology
Yuelin Zhu MSc 100104-Pathology and Pathophysiology
Mingming Fan Ph.D. 100104-Pathology and Pathophysiology
Shanshan Zhang MSc 077804-Pathology and Pathophysiology
Yuan Xie MSc 077804-Pathology and Pathophysiology
Wenlong Li Ph.D. 100104-Pathology and Pathophysiology
Hongyu Wu Ph.D. 100104-Pathology and Pathophysiology
Yun Yang Ph.D. 100104-Pathology and Pathophysiology