Yuan Wang, PhD

yuan wang

Email:  wangyu81@msu.edu
Phone: 517-353-1416

Education/Training Information

  • Bachelor in Medicine, Shangdong Medical University, China
  • MS, Chinese Academy pf Preventive Medicine, China
  • PhD, Boston University, USA
  • Post-doc, Harvard Medical School and NIEHS

Award

1997-98    Presidential Award, Boston University

1998-02   Research Fellowship, Boston University

2003-05   National Research Service Award, NIH

2004        Travel Award for the American Society of Hematology Annual Meeting  

2005        Charles Terner Award for Research Excellence, Boston University

2006        Fellows Award for Research Excellence, NIH

2015        Travel Award for ISSCR annual meeting, Stockholm, Sweden

 

Research Interests

The initial germ cell population, known as primordial germ cells (PGCs), arises from proximal epiblast around embryonic day 7 in mice. These PGCs subsequently migrate to the genital ridge. In male, PGCs become spermatogonia and eventually develop into sperm after birth. Disrupting this process causes male infertility. My main research focus is to dissect the regulatory programs that govern mammalian germ cell development. Specifically, I am interested in understanding how PGCs diverge from somatic lineages to establish germline competency in embryos, and how developmental cues and metabolic needs are intertwined at mitochondria to regulate spermatogonial fate decision to become sperm after birth. Empowered with in vitro differentiation platforms of pluripotent stem cells and spermatogonial stem cells, as well as in vivo genetically modified mouse models, my laboratory aims to improve our knowledge in mammalian reproduction, thereby informing the underlying genetic causes of human male infertility.

BRG1-SWI/SNF complex affects the pluripotency of human embryonic stem cells

yuan bio We have broad interest in cellular events that regulate self-renewal and differentiation of pluripotent and germline stem cells. For example, the SWI/SNF is a chromatin remodeling complex that that contains either BRG1 or BRM exclusively as the catalytic ATPase subunit that drives the alteration of DNA-nucleosome structure and thus regulates gene transcription. We identified a unique composition of the SWI/SNF complex in human pluripotent stem cells (PSCs) by containing BRG1, BAF250A, BAF170, BAF155, BAF53A, and BAF47. We found that BRG1-SWI/SNF complex played a repressive role in transcriptional regulation by inhibiting the acetylation levels of H3K27 at the enhancers of lineage specific genes from human PSCs (Stem Cell Reports, 2014).

Understanding germ cell development and male infertility using stem cell in vitro differentiation system and genetically modified mouse models

yuan bio1We have established an in vitro differentiation protocol of human and mouse PSCs toward germ cells. Empowered with iPSC technology, in vivo mouse knockout models, and long-term in vitro culture system of spermatogonial stem cells, we aim to dissect the genetic programs that govern germ cell development. The knowledge gained from these studies will greatly improve our understanding of the underlying biology of human male infertility.

Selected Publications (* corresponding author):

  1. Chen W, Zhang Z, Chang C, Yang Z, Wang P, Fu H, Wei X, Chen E, Tan S, Huang W, Sun L, Ni T, Yang Y & Wang Y*. (2020) A bioenergetic shift is required for spermatogonial differentiation. Cell Discovery 6:56.
  2. Wang S, Wang P, Liang D & Wang Y*. BRG1 Is Dispensable for Sertoli Cell Development and Functions in Mice. (2020) Int J Mol Sci 21(12).
  3. Chen W, Sun Y, Sun Q, Zhang J, Jiang M, Chang C, Huang X, Wang C, Wang P, Zhang Z, Chen X & Wang Y*. MFN2 Plays a Distinct Role from MFN1 in Regulating Spermatogonial Differentiation. (2020) Stem Cell Reports. 14(5):803-817
  4. Fan KQ, Li YY, Wang HL, Mao XT, Guo JX, Wang F, Huang LJ, Li YN, Ma XY, Gao ZJ, Chen W, Qian DD, Xue WJ, Cao Q, Zhang L, Shen L, Zhang L, Tong C, Zhong JY, Lu W, Lu L, Ren KM, Zhong G, Wang Y, Tang M, Feng XH, Chai RJ, Jin J. Stress-Induced Metabolic Disorder in Peripheral CD4(+) T Cells Leads to Anxiety-like Behavior. (2019) Cell 179(4):864-79
  5. Zhao Y, Ye S, Liang D, Wang P, Fu J, Ma Q, Kong R, Shi L, Gong X, Chen W, Ding W, Yang W, Zhu Z, Chen H, Sun X, Zhu J, Li Z & Wang Y*. In Vitro Modeling of Human Germ Cell Development Using Pluripotent Stem Cells. (2018) Stem Cell Reports 10(2):509-23.
  6. Tang C, Wang Q, Su J, Ting N, Yang W, Wang Yo, Chen W, Liu X, Wang S, Zhang J, Song H, Zhu J & Wang Y*.(2017) NRF1 Coordinates with DNA methylation to regulate spermatogenesis, FASEB J31(11):4959-4970
  7. Gong X, Chao R, Wang P, Huang X, Zhang J, Zhu X, Zhang Y, Yang X, Hou C, Ji X, Shi T & Wang Y*.(2017) Interplay of transcription factors and microRNAs during embryonic hematopoiesis, SCI China Life Science60 (2):168-177
  8. Zhang J, Wang Q, Wang M, Jiang M, Wang YS, Sun Y, Xie TR, Wang J, Tang N, Song H, Chao R, Chen X & Wang Y*. (2016) GASZ and MFN-mediated mitochondrial functions are crucial for spermatogenesis, EMBO Rep17:220-34
  9. Chao R, Gong X, Wang L, Wang P & Wang Y*(2015) CD71high population represents primitive erythroblasts derived from mouse embryonic stem cells, Stem Cell Res14 (1):30-38
  10. Chu M, Wang L, Wang H, Ni T, Zhu J & Wang Y*.(2014) A novel role for CDX1 in embryonic epicardial development, PLoS ONE9 (7): e103271
  11. Zhang X, Li B, Li W, Ma L, Zheng D, Li L,Yang W, Chu M, Chen W, Mailman R, Zhu J, Fan G, Archer TK & Wang Y*.(2014) Transcriptional repression by BRG1-SWI/SNF complex affects pluripotency of human embryonic stem cells, Stem Cell Reports3:460-474
  12. Cui H, Wang Y, Huang H, Yu W, Bai M, Zhang L, Bryan BA, Wang Y, Luo J, Li D, Ma Y & Liu M. (2014). GPR126 Regulates Developmental and Pathological Angiogenesis through Modulation of VEGFR2 Signaling. J Biol Chem.289:34871-85
  13. Wang Q, Liu XQ, Tang N, Archambeault D, Li J, Song H, Tang C, He B, Matzuk M & Wang Y*.(2013) GASZ promotes germ cell derivation from embryonic stem cells. Stem Cell Res11(2):845-860
  14. Wu Z, Yang M, Liu H, Hongchao G, Wang Y,Cheng H & Chen L. (2012)Role of nuclear receptor co-activator 3 (Ncoa3) in pluripotency maintenance. Biol Chem.287(45):38295-304
  15. de Jong JL, Davidson AJ, Wang Y,Palis J, Opara P, Pugach E, Daley GQ & Zon LI. (2010) Interaction of retinoic acid and scl controls primitive blood development,Blood116 (2): 201-209
  16. Koo S, Huntly BJ , Wang Y,Chen J, Brumme K, Ball B, McKinney-Freeman SL, Yabuuchi A, Scholl C, Bansal D, Zon LI, Fröhling S, Daley GQ, Gilliland G & Mercher T. (2010) Cdx4 is dispensable for murine adult hematopoietic stem cells, but promotes MLL-AF9-mediated leukemogenesis. Haematologica95 (10): 1642-1650
  17. Wang Y,Yabuuchi A, McKinney-Freeman S, Ducharm, Ray M, Chawengsaksophak K, Trevor Archer & Daley GQ. (2008) Cdxgene deficiency compromises embryonic hematopoiesis in the mouse, PNAS 105: 7756-61
  18. McKinney-Freeman S, Lengerke C, Jang IH, Shea J, Wang Y,Schmitt S,Philitas M, Shae J & Daley GQ. (2008) Modulation of murine embryonic stem cell-derived CD41+c-kit+ hematopoietic progenitors by ectopic expression of Cdx genes, Blood 111(10):4944-53
  19. Wang Y,Yates F, Naveiras O, Ernst P & Daley GQ. (2005) Embryonic stem cell-derived hematopoietic stem cells. PNAS102(52):19081-6.
  20. Davidson AJ, Ernst P, Wang Y, Dekens MPS, Kinglsey PD, Palis J, Korsmeyer SJ, Daley GQ & Zon LI. (2003) Cdx4 mutants fail to specify haematopoietic progenitors during embryogenesis and can be rescued by multiple hox genes. Nature425(6955): 300-6.
  21. Wang Y& Gilmore TD. (2003) Zyxin and paxillin proteins: focal adhesion plaque LIM domain proteins go nuclear. Biochimica Biophysica Acta1593:115-20.
  22. Wang Y& Gilmore TD. (2001) LIM domain protein Trip6 has a conserved nuclear export signal, nuclear targeting sequences, and multiple transactivation domains. Biochimica Biophysica Acta1538: 260-272.
  23. Wang Y, Dooher JE, Koedood-Zhao M & Gilmore TD. (1999) Characterization of mouse Trip6: a putative intracellular signaling protein. Gene234: 403-409.

NCBI Publications