A major accomplishment during embryonic development is the generation of cellular diversity and orderly organization of the cell types in a basic plan that serves as the blueprint for embryogenesis and morphogenesis. This hierarchy of cell orders, i.e. the cell lineage, is a tightly controlled and well-coordinated process marked by a series of cell fate decisions during embryo development. To resolve the spatial organization and molecular architecture underpinning the cell lineage segregation in mouse embryos, we developed a method to systematically survey the spatial organization of tissue cell types, named Geo-seq. This method can be implemented to investigate the transcriptome landscape in sections of the native tissues with high efficiency and accuracy, and preserve the spatial information (Nature Protocols, 2017). Using Geo-seq, the temporal and spatial regulation for the stem cell fates commitment and specification in early mouse embryos were unraveled in unprecedented details (Developmental Cell, 2016). Our study provided high resolution digital in situ hybridization attributes, defined the molecular genealogy of germ layers and continuum of pluripotent states in real time and real space resolution. The spatial-temporal transcriptome further revealed the molecular determinants that drive lineage specification and germ layer development, and uncovered the stem cell lineage differentiation in unprecedented details (Nature, 2019). This analysis also provided de novo spatial coordinates to enable single cell positional mapping.

To fulfill the needs of high-throughput single cell sequencing and spatial transcriptomic profiling, we combined the cell barcoding and in situ positional indexing with platforms such as automatic liquid processing and microfluid. We established an automatic scRNA-seq toolkit (Auto-seq) and multi-dimensional spatial -omics technologies (mi-Step). Using Auto-seq, we comprehensively examined the single cell developmental trajectories of post-implantation embryo and retrospectively mapped the single cell’s location (Nature, 2019). With the help of these new tools, we have elucidated the lineage trajectory for pluripotent cell differentiation during germ layer development in single cell resolution and characterized the progenitor cell population residing the lung epithelium (Nature Genetics, 2019). 

PhD of Shanghai Institute of Biochemistry and Cell Biology

   

Developmental Biology

Sequencing and informatics technologies in biomedical research

Corresponding author or first author papers:

1.     Peng G*#, Suo S#, Cui G#, Yu F#, Wang R, Chen J, Chen S, Liu Z, Chen G, Qian Y, Tam PPL, Han JJ*, Jing N* (2019) Molecular architecture of lineage allocation and tissue organization in early mouse embryo. Nature, 572: 528–532 (F1000 Recommend)

2.     Liu Q, Liu K, Cui G, Huang X, Yao S, Guo W, Qin Z, Li Y, Yang R, Pu W, Zhang L, He L, Zhao H, Yu W, Tang M, Tian X, Cai D, Nie Y, Hu S, Ren T, Qiao Z, Huang H, Zeng YA, Jing N, Peng G*, Ji H*, Zhou B* (2019) Lung regeneration by multipotent stem cells residing at the bronchioalveolar-duct junction. Nature Genetics, 51: 728–738

3.     Peng G^#, Suo S^#, Chen J^#, Chen W, Liu C, Yu F, Wang R, Chen S, Sun N, Cui G, Song L, Tam PPL, Han J-DJ & Jing N (2016) Spatial Transcriptome for the Molecular Annotation of Lineage Fates and Cell Identity in Mid-gastrula Mouse Embryo. Developmental Cell 36, 681–697. (Feature Article, Most read paper)

4.     Chen J, Suo S, Tam PP, Han J-DJ*, Peng G* & Jing N* (2017) Spatial transcriptomic analysis of cryosectioned tissue samples with Geo-seq. Nature Protocols 12, 566–580. 

5.     Peng, G*., Cui, G., Ke, J. and Jing, N*. (2020) Using Single-Cell and Spatial Transcriptomes to Understand Stem Cell Lineage Specification During Early Embryo Development. Annu Rev Genomics Hum Genet, 21, 163-181

6.     Xia, Q.#, Cui, G.#, Fan, Y., Wang, X., Hu, G., Wang, L., Luo, X., Yang, L., Cai, Q., Xu, K., Guo, W., Gao, M., Li, Y., Wu, J., Li, W., Chen, J., Qi, H., Peng, G*. and Yao, H*. (2021) RNA helicase DDX5 acts as a critical regulator for survival of neonatal mouse gonocytes. Cell Prolif 54, e13000.

7.     Cui G, Jing N, Peng G* (2019) Comments on ‘Molecular architecture of lineage allocation and tissue organization in early mouse embryo’. Journal of Molecular Cell Biology, 11, 1024-1025.

8.     Peng G, Han JJ (2018) Regulatory network characterization in development: challenges and opportunities. F1000Res, 7:

9.     Han, X^#, Luo, S^#, Peng G^#, Lu, JY, Cui G, Liu L, Yan P, Yin Y, Liu W, Wang R, Chang Z, Na J, Jing N^*, and Shen X^* (2018). Mouse knockout models reveal largely dispensable but context-dependent functions of lncRNAs during development. Journal of Molecular Cell Biology. 10:175-178. 

10.  Cui G, Suo S, Wang R, Qian Y, Han JJ, Peng G^*, Tam PPL^*, Jing N^* (2018) Mouse gastrulation: Attributes of transcription factor regulatory network for epiblast patterning. Dev Growth Differ, 60: 463–472

11.  Peng G (2017) Looking Back: Single-Cell Analysis, Empowering Stem Cell Studies (2017) Cell Stem Cell 20: 758 (Commentary)

12.  Peng G, Tam P & Jing N (2017) Lineage specification of early embryos and embryonic stem cells at the dawn of enabling technologies. National Science Review. doi:10.1093/nsr/nwx093

13.  Peng G* & Jing N* (2017) The genome-wide molecular regulation of mouse gastrulation embryo. Science China Life Science. doi:10.1007/s11427-016-0285-3 

14.  Peng G &Jing N (2016) Early embryo development and lineage determination. Chinese Bulletin of Life Sciences.

co-authored papers:

1.      Niu Y, Sun N, Li C, Lei Y, Huang Z, Wu J, Si C, Dai X, Liu C, Wei J, Liu L, Feng S, Kang Y, Si W, Wang H, Zhang E, Zhao L, Li Z, Luo X, Cui G, Peng G, Izpisúa Belmonte JC, Ji W, Tan T (2019) Dissecting primate early post-implantation development using long-term in vitro embryo culture. Science, 366: doi:10.1126/science.aaw5754

2.      Shim, W.J., Sinniah, E., Xu, J., Vitrinel, B., Alexanian, M., Andreoletti, G., Shen, S., Sun, Y., Balderson, B., Boix, C., Peng, G., Jing, N., Wang, Y., Kellis, M., Tam, P.P.L., Smith, A., Piper, M., Christiaen, L., Nguyen, Q., Bodén, M. and Palpant, N.J. (2020) Conserved Epigenetic Regulatory Logic Infers Genes Governing Cell Identity. Cell Syst 11, 625-639.e13.

3.      Kim, H.J., Osteil, P., Humphrey, S.J., Cinghu, S., Oldfield, A.J., Patrick, E., Wilkie, E.E., Peng, G., Suo, S., Jothi, R., Tam, P.P.L. and Yang, P. (2020) Transcriptional network dynamics during the progression of pluripotency revealed by integrative statistical learning. Nucleic Acids Res 48, 1828-1842.

4.      Zhang, K., Yu, F., Zhu, J., Han, S., Chen, J., Wu, X., Chen, Y., Shen, T., Liao, J., Guo, W., Yang, X., Wang, R., Qian, Y., Yang, J., Cheng, L., Zhao, Y., Hui, C.C., Li, J., Peng, G., He, S., Jing, N. and Tang, K. (2020) Imbalance of Excitatory/Inhibitory Neuron Differentiation in Neurodevelopmental Disorders with an NR2F1 Point Mutation. Cell Rep 31, 107521.

5.      He, D.D., Tang, X.T., Dong, W., Cui, G., Peng, G., Yin, X., Chen, Y., Jing, N. and Zhou, B.O. (2020) C-KIT Expression Distinguishes Fetal from Postnatal Skeletal Progenitors. Stem Cell Reports doi:10.1016/j.stemcr.2020.03.001

6.      Yang X, Hu B, Liao J, Qiao Y, Chen Y, Qian Y, Feng S, Yu F, Dong J, Hou Y, Xu H, Wang R, Peng G, Li J, Tang F, Jing N (2019) Distinct enhancer signatures in the mouse gastrula delineate progressive cell fate continuum during embryo development. Cell Research, 29: 911–926

7.      Zhou Y, Wang X, Song M, He Z, Cui G, Peng G, Dieterich C, Antebi A, Jing N, Shen Y (2019) A secreted microRNA disrupts autophagy in distinct tissues of Caenorhabditis elegans upon ageing. Nature Communications, 10: 4827

8.      Yu W, Ma X, Xu J, Heumüller AW, Fei Z, Feng X, Wang X, Liu K, Li J, Cui G, Peng G, Ji H, Li J, Jing N, Song H, Lin Z, Zhao Y, Wang Z, Zhou B, Zhang L (2019) VGLL4 plays a critical role in heart valve development and homeostasis. PLoS Genetics, 15: e1007977

9.      Song W, Wang R, Jiang W, Yin Q, Peng G, Yang R, Yu QC, Chen J, Li J, Cheung TH, Jing N, Zeng YA (2019) Hormones induce the formation of luminal-derived basal cells in the mammary gland. Cell Research, 29: 206–220

10.   Cheng S, Pei Y, He L, Peng G, Reinius B, Tam PPL, Jing N, Deng Q (2019) Single-Cell RNA-Seq Reveals Cellular Heterogeneity of Pluripotency Transition and X Chromosome Dynamics during Early Mouse Development. Cell Reports, 26: 2593–2607.e3

11.   Osteil P, Studdert JB, Goh HN, Wilkie EE, Fan X, Khoo PL, Peng G, Salehin N, Knowles H, Han JJ, Jing N, Fossat N, Tam PPL (2019) Dynamics of Wnt activity on the acquisition of ectoderm potency in epiblast stem cells. Development, 146, doi:10.1242/dev.172858

12.   Xue Y, Liu D, Cui G, Ding Y, Ai D, Gao S, Zhang Y, Suo S, Wang X, Lv P, Zhou C, Li Y, Chen X, Peng G, Jing N, Han JJ, Liu F (2019) A 3D Atlas of Hematopoietic Stem and Progenitor Cell Expansion by Multi-dimensional RNA-Seq Analysis. Cell Reports, 27: 1567–1578.e5

13.   Friedman CE, Nguyen Q, Lukowski SW, Helfer A, Chiu HS, Miklas J, Levy S, Suo S, Han JJ, Osteil P, Peng G, Jing N, Baillie GJ, Senabouth A, Christ AN, Bruxner TJ, Murry CE, Wong ES, Ding J, Wang Y, Hudson J, Ruohola-Baker H, Bar-Joseph Z, Tam PPL, Powell JE, Palpant NJ (2018) Single-Cell Transcriptomic Analysis of Cardiac Differentiation from Human PSCs Reveals HOPX-Dependent Cardiomyocyte Maturation. Cell Stem Cell, 23: 586–598.e8

14.   Christodoulou N, Kyprianou C, Weberling A, Wang R, Cui G, Peng G, Jing N, Zernicka-Goetz M (2018) Sequential formation and resolution of multiple rosettes drive embryo remodelling after implantation. Nature Cell Biology, 20: 1278–1289

15.   Sibbritt, T., Ip, C. K., Khoo, P. L., Wilkie, E., Jones, V., Sun, J. Q. J., Shen, J. X., Peng, G., Han, J. J., Jing, N., Osteil, P., Ramialison, M., Tam, P. P. L., and Fossat, N. (2018). A gene regulatory network anchored by LIM homeobox 1 (LHX1) for embryonic head development. Genesis 56: e23246

16.   Liu C, Wang, R, He Z, Osteil P, Yang X, Chen J, Peng G, Tam P, Jing N (2018), Suppressing Nodal Signaling Activity Predisposes Ectodermal Differentiation of Epiblast Stem Cells. Stem Cell Reports 11, 43-57.

17.   Yang X, Hu B, Hou Y, Qiao Y^,, Wang R, Chen Y, Qian Y, Feng S, Chen J, Liu C, Peng G, Tang F and Jing N (2018). Silencing of developmental genes by H3K27me3 and DNA methylation reflects the discrepant plasticity of embryonic and extraembryonic lineages. Cell Research 28(5):593-596.

18.   Liu, C., Peng, G., and Jing, N. (2018). TGF-β signaling pathway in early mouse development and embryonic stem cells. Acta Biochim Biophys Sin. 50, 68-73.

19.   Zamir L, Singh R, Nathan E, Patrick R, Yifa O, Yahalom-Ronen Y, Arraf AA, Schultheiss TM, Suo S, Han J-DJ, Peng G, Jing N, Wang Y, Palpant N, Tam PP, Harvey RP & Tzahor E (2017) Nkx2.5 marks angioblasts that contribute to hemogenic endothelium of the endocardium and dorsal aorta. elife 6, e20994.

20.   Song L, Chen J, Peng G, Tang K & Jing N (2016) Dynamic Heterogeneity of Brachyury in Mouse Epiblast Stem Cells Mediates Distinct Response to Extrinsic Bone Morphogenetic Protein (BMP) Signaling. Journal of Biological Chemistry 291, 15212–15225.

21.   Tang K, Peng G, Qiao Y, Song L & Jing N (2015) Intrinsic regulations in neural fate commitment. Development, Growth&Differentiation. 57, 109–120.

22.   Li L, Song L, Liu C, Chen J, Peng G, Wang R, Liu P, Tang K, Rossant J & Jing N (2015) Ectodermal progenitors derived from epiblast stem cells by inhibition of Nodal signaling. Journal of Molecular Cell Biology 7, 455–465.

23.   Liu P, Dou X, Peng G, Han J-DJ & Jing N (2015) Genome-wide analysis of histone acetylation dynamics during mouse embryonic stem cell neural differentiation. Genomic Data 5, 15–16.

24.   Song L, Sun N, Peng G, Chen J, Han J-DJ & Jing N (2015) Genome-wide ChIP-seq and RNA-seq analyses of Pou3f1 during mouse pluripotent stem cell neural fate commitment. Genomic Data 5, 375–377.

25.   Liu P, Dou X, Liu C, Wang L, Xing C, Peng G, Chen J, Yu F, Qiao Y, Song L, Wu Y, Yue C, Li J, Han J-DJ, Tang K & Jing N (2015) Histone deacetylation promotes mouse neural induction by restricting Nodal-dependent mesendoderm fate. Nature Communications 6, 6830.

26.   Zhu Q, Song L, Peng G, Sun N, Chen J, Zhang T, Sheng N, Tang W, Qian C, Qiao Y, Tang K, Han J-DJ, Li J & Jing N (2014) The transcription factor Pou3f1 promotes neural fate commitment via activation of neural lineage genes and inhibition of external signaling pathways. elife 3, 2.

27.   Li G, Bahn JH, Lee J-H, Peng G, Chen Z, Nelson SF & Xiao X (2012) Identification of allele-specific alternative mRNA processing via transcriptome sequencing. Nucleic Acids Research 40, e104–e104.

28.   Bahn JH, Lee J-H, Li G, Greer C, Peng G & Xiao X (2012) Accurate identification of A-to-I RNA editing in human by transcriptome sequencing. Genome Research 22, 142–150.

29.   Lee J-H, Gao C, Peng G, Greer C, Ren S, Wang Y & Xiao X (2011) Analysis of transcriptome complexity through RNA sequencing in normal and failing murine hearts. Circulation Research 109, 1332–1341.

30.   Kong L, Choi RCY, Xie HQ, Wang X, Peng G, Xie Z, Tsim KWK & Jing N (2011) Expression of the IgSF protein Kirre in the rat central nervous system. Life Sciences 88, 590–597.

Implementing cutting-edge technologies to investigate the regulatory mechanisms of stem cell lineage segregation and promoting the translational application of functional stem cells.