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Yan-Ling WANG, Ph. D.

Regulation of placental development, pregnancy adaptation, and the pathogenesis of pregnancy disorders (preeclampsia and recurrent spontaneous abortion) derived from placental defects.


Staffs: Yu-Xia Li, Xuan Shao
PhD Candidates: Xiaotao Bian, Zhilang Li, Yeling Ma, Juan Liu, Feiyang Wang, Xin Yu, Mingming Fan, Hongyu Wu, Yun Yang, Yuelin Zhu, Qianqian Li

· WANG Group website

 

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 elusive. The prediction, prevention, and treatment of the placenta-associated pregnant diseases are also urgently needed.

We integrate clinical resource and multiple in vitro and in vivo research models to investigate the mechanisms underlying the construction of placental functional units including blood perfusion, nutrient metabolism, immune tolerance and pregnancy adaptation.

We have established and maintained several in vitro models, including the culture system for human trophoblastic cells at different differentiation pathways, three-dimensional co-culture of trophoblasts-endothelial cells, trophoblast stem 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. A prospective resource bank of pregnant diseases has been established through collaboration with multi-center clinical units. A batch of molecular markers for early diagnosis of preeclampsia were obtained. The mechanisms underlying the construction of placental functional units including blood perfusion, nutrient metabolism, immune tolerance and pregnancy adaptation were studied by comparing the physiological and pathological placentas.

Xuan Shao: Assistant professor, Dr. Shao received his B.A. in Biology from Hebei University, M.A. in pharmacology from Academy of Military Medical Sciences, Ph. D. in Developmental Biology from Institute of Zoology, Chinese Academy of Sciences. Dr. Shao’s main research interest is pregnancy adaptation and trophoblast metabolism. He has published 8 papers in peer-reviewed journals including PNAS, Hypertension, Cell Proliferation, Journal of Hypertension and Biology of Reproduction as first author/co-first author or corresponding author. Dr. Shao has been supported by grant from the National Natural Science Foundation of China and participated in three key R&D plans. Dr. Shao is a reviewer of BMC pregnancy & Childbirth and Chinese Journal of Zoology.



Placental trophoblast syncytialization potentiates macropinocytosis via mTOR signaling to adapt to reduced amino acid supply



The mechanisms of the spiral artery remodeling in human placenta



Single-Cell Immune Landscape of Human Recurrent Miscarriage



Quantitative chemoproteomics reveals O-GlcNAcylation of Cystathionine γ-lyase (CSE) represses trophoblast syncytialization

 

Research content and objectives:

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.

 

Selected publications:

  1. 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. Proc Natl Acad Sci U S A. 2020
  2. Wang F#, Jia W#, Fan M#, Shao X#, Li Z, Liu Y, Ma Y, Li YX, Li R*, Tu Q*, Wang YL *. Single-cell immune landscape of human recurrent miscarriage. Genomics Proteomics and Bioinformatics. 2020
  3. 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
  4. 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. 2020
  5. 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
  6. 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, 53:e12802.
  7. 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, 102(3), 560–570.
  8. 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. J Hypertension, 2019, 37:197–205.
  9. Li G#, Ma L#, Lu H#, Cao G, Shao X, Liu Y, Li YX, Liu M, Yang H, Wang YL*. Transactivation of Met signalling by semaphorin4D in human placenta: implications for the pathogenesis of preeclampsia. J Hypertension. 2018, 36(11):2215-2225.
  10. 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, 99(3):476-478.
  11. 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 X, Huang Y, Xiao R, 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, 115(26):E5896-E5905.
  12. 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.
  13. Shao X#, Liu Y#, Liu M, Wang Y, Yan L, Wang H, Ma L, Lia YX, Zhao Y*, Wang YL· WANG Group website*. Testosterone represses estrogen signaling via upregulating mir-22: mechanism for imbalanced steroid hormone production in preeclampsia. Hypertension, 2017, 69:721-730. (Editorial highlight)
  14. Luo R#, Shao X#, Xu P, Liu Y, Wang Y, Zhao Y, Liu M, Ji L, Li YX, Chang C, Qiao J, Peng C*, Wang YL*. MicroRNA-210 contributes to preeclampsia by down-regulating KCMF1. Hypertension, 2014 64:839-847
  15. Xu P#, Zhao Y#, Liu M, Wang Y, Wang H, Li YX, Zhu X, Yao Y, Wang H, Qiao J, Ji L*, Wang YL*. Variations of micrornas in human placentas and plasma from preeclamptic pregnancy. Hypertension, 2014, 63:1276-1284.
  16. Burton GJ*, Sebire NJ, Myatt L, Tannetta D, Wang YL, Sadovsky Y, Staff AC, Redman CW (2014). Optimising sample collection for placental research. Placenta, 35(4):289-303
  17. Ji L#, Brkic J#, Liu M#, Fu G, Peng C*, Wang YL*. Placental trophoblast cell differentiation: physiological regulation and pathological relevance to preeclampsia. Mol Asp Med, 2013,34:981-1023.