Possible Rotation Projects:
Temporal and spatial analysis of mouse heart development at single cell level. Multiplexed single cell mRNA sequencing will be used to analyze the mouse cardiac cells from the very beginning to the early postnatal stages to understand the molecular and cellular features of cardiac cells.
In vitro modeling human congenital heart defects (CHDs). 3D differentiation system will be used to guide the human disease patient and control patient iPSCs into cardiac cell lineages, and single cell mRNA sequencing and other molecular assays will be further used to characterize these cells to identify the molecular defects in CHDs.
Tissue clearing, light sheet imaging, and spatial molecular sequencing will be combined to understand the genes expression in situ with single molecular resolution in the developing mouse hearts.
Training Technologies Used:
Transgenic mouse models; Human iPSCs; Single cell mRNA sequencing; Single molecular in situ hybridization; Machine learning (Randomforest); CRISPR/Cas9; Lightsheet microscope; Tissue clearing.
- B.S., Nanchang University, China- 2007
- Ph.D.,Chinese Academy of Sciences- 2012
- Postdoc-Stanford University-2017
- Instructor-Stanford University-2019
Li G.,* Tian L., Goodyer W., Kort E., Buikema J., Xu A., Wu J., Jovinge S. *, Wu SM* (2019) Single cell expression analysis reveals anatomical and cell cycle-dependent transcriptional shifts during heart development. Development. PMID: 31142541 *Corresponding author.
Li G.,* Xu A.,* Sim S, Priest J., Tian X., Khan T., Quertermous T., Zhou B., Tsao P., Quake S., Wu S.M. (2016) Transcriptomic profiling maps anatomically patterned subpopulations among single embryonic cardiac cells. Developmental Cell. PMID: 27840109. *Equal contribution.
Li G., Plonowska K., Kuppusamy R., Sturzu A., Wu S.M. (2015) Identification of cardiovascular lineage descendants at single cell resolution. Development. PMCID: PMC4352984
Sharma A.*, Li G.*, Kuppusamy R.*, Hamaguchi R., Burridge P., Wu S.M. (2015) Derivation of highly purified cardiomyocytes from human induced pluripotent stem cells using small molecule-modulated differentiation and subsequent glucose starvation. J Vis Exp. PMID: 25867738. *Equal contribution.
Tabula Muris Consortium; Overall coordination; Logistical coordination; Organ collection and processing; Library preparation and sequencing; Computational data analysis; Cell type annotation; Writing group; Supplemental text writing group; Principal investigators. (2018) Single-cell transcriptomics of 20 mouse organs creates a Tabula Muris. Nature. PMID: 30283141.
Su T., Stanley G., Sinha R., D’Amato G., Das S., Rhee S., Chang AH., Poduri A., Raftrey B., Dinh TT., Roper WA., Li G., Quinn KE., Caron KM., Wu SM., Miquerol L., Butcher EC, Weissman I., Quake S., Red-Horse K (2018) Single-cell analysis of early progenitor cells that build coronary arteries. Nature. PMID: 29973725
Li G., Dzilic E., Flores N., Shieh A., Wu S.M. (2017) Strategies for the acquisition of transcriptional and epigenetic information in single cells. Journal of Thoracic Disease. PMID: 28446964.
Gregoire S, Li G., Sturzu AC, Schwartz RJ, Wu S.M. (2017) YY1 Expression Is Sufficient for the Maintenance of Cardiac Progenitor Cell State. Stem Cells. PMID: 28580685
Sturzu A., Rajarajan K., Passer D., Plonowska K., Riley A., Tan T., Sharma A., Engels M., Feistritzer R., Li G., Selig M., Geissler R., Xu A., Robertson K., Scherrer-Crosbie M., Domian I., Wu S.M. (2015) Fetal Mammalian Heart Generates a Robust Compensatory Response to Cell Loss. Circulation. PMID: 25995316.
Chuang W, Sharma A, Shukla P, Li G., Mall M, Rajarajan K, Abilez O.J., Hamaguchi R, Wu J.C., Wernig M, Wu S.M. (2017) Partial Reprogramming of Pluripotent Stem Cell-Derived Cardiomyocytes into Neurons. Scientific Reports. PMID: 28327614.
Heart development as a critical embryonic developmental process is tightly regulated on the cellular and molecular level. If this process goes awry, it will lead to congenital heart diseases (CHD), which accounts for a significant portion of stillbirths and is present in 1-2% of all live births. We are using advanced techniques including human induced pluripotent stem cells (hiPSC), single-cell RNA sequencing, single molecular in situ hybridization, CRISPR/Cas9, and tissue cleaning methods to decode the spatial and temporal information of each single cardiac cells. Meanwhile, with the knowledge gained from the study of basic cardiac lineage regulations, the lab is also exploring the lineage defects in congenital heart diseases using patient-derived iPSCs.
