This grant has enabled a plethora of activities in California Stem Cell Genomics. The Stanford Administrative Core for the Center of Excellence in Stem Cell Genomics (CESCG) has been established and is responsible for overseeing joint center activities, and the administration of center-initiated projects (CIP) 1 and 2, and several collaborative research projects (CRP). In the first year of the award the CESCG administration organized monthly telephone conference calls to share research progress and coordinate activities across the Center. On May 1, 2015 the CESCG held its first center-wide retreat in a one-day event at Clark Center on the campus of the Stanford Medical School. The two CIPs have made significant progress. CIP1 has generated a valuable resource of 38 induced pluripotent stem cell lines and established a reliable platform for high throughput derivation of human induced pluripotent stem cell-derived cardiomyocytes for use in downstream high throughput toxicity and drug pharmacology screening assays. CIP2 has completed the first human single cell brain analysis and is in the process of deriving a single cell pancreatic map. We have launched our collaborative research progress grant. Following on the receipt of applications in October 2014 and successful review in January 2015, the Administrative Core at Stanford has also issued subcontract awards for 3 CRPs managed by the CESCG from the Northern California site – two comprehensive project awards CRP-C2 to Daniel Geschwind of UCLA and CRP-C3 to Arnold Kriegstein of UCSF, and a regular project award CRP-R4 to Jeremy Sanford of UCSC. These activities will transform stem cell research in California and continue its preeminence in this area.
Reporting Period:
Year 2
This grant has enabled a plethora of activities pertaining to stem cell genomics in the state of California. The Stanford Administrative Core for the Center of Excellence in Stem Cell Genomics (CESCG) has been established and is responsible for overseeing joint center activities and the administration of center-initiated projects (CIP) 1 and 2, and several collaborative research projects (CRP). In the second year of the award the CESCG administration organized monthly telephone conference calls to share research progress and coordinate activities across the center. On April 29, 2016 the CESCG held its second center-wide retreat in a one-day event at Salk Institute. The two CIPs have made significant progress. CIP1 has recruited 102 donors and generated a valuable resource of 71 induced pluripotent stem cell lines. Whole genome sequencing from the first batch of 10 iPSCs has been completed and data analysis is underway. CIP1 has also started differentiating an initial set of iPSCs into cardiomyocytes and treated them with various drugs. RNA-seq is underway to detect the effects of drug treatment. CIP2 has completed the first human single cell brain analysis and is finishing the derivation of a single cell fetal and adult pancreatic map. We have also launched our second call of CRP grants. Following receipt of call 2 applications on October 30, 2015 and successful review on January 15, 2016, the Administrative Core at Stanford has issued subcontract awards to four CRPs that will be managed by the Northern California CESCG site. The principal investigators of these CRPs are Jacob Corn from Berkeley, Jeanne Loring from Scripps, Irving Weissman from Stanford, and Gene Yeo from UCSD. These research projects from the CIPs and CRPs will transform stem cell research in California and continue its preeminence in this area.
Reporting Period:
Year 3
This grant has enabled a plethora of activities pertaining to stem cell genomics in the state of California. The Stanford Administrative Core for the Center of Excellence in Stem Cell Genomics (CESCG) has been established and is responsible for overseeing joint center activities and the administration of center-initiated projects (CIP) 1 and 2, and several collaborative research projects (CRP). In the third year of the award the CESCG administration organized monthly telephone conference calls to share research progress and coordinate activities across the center. On April 20th-21st, 2017 the CESCG held its third annual stem cell genomic CIRM retreat at Stanford University. CIP1 has collected 180 blood samples in total and generated a valuable resource of 164 induced pluripotent stem cell lines. Whole genome sequencing from the first batch of 34 iPSCs has been completed and data analyzed. CIP1 has also differentiated 26 iPSCs into cardiomyocytes and treated them with various drugs followed by RNA-Seq. CIP2 has managed to establish a workflow for Patch-seq in an effort to couple cell function and genomics and in situ methods to localize the candidates identified previously from RNAseq of primary tissues. In addition, they posted a manuscript to Bioarxiv that presents results from the analysis of fetal and adult pancreatic tissue, and another manuscript that describes infiltrating cells in glioblastoma is under review. All other CRP collaborators have made a significant progress in their projects. These research projects from the CIPs and CRPs will transform stem cell research in California and continue its preeminence in this area.
Reporting Period:
Year 4
This grant has enabled a plethora of activities pertaining to stem cell genomics in the state of California. The Stanford Administrative Core for the Center of Excellence in Stem Cell Genomics (CESCG) has been established and is responsible for overseeing joint center activities and the administration of center-initiated projects (CIP) 1 and 2, and several collaborative research projects (CRP). In the fourth year of the award the CESCG administration organized monthly telephone conference calls to share research progress and coordinate activities across the center. On May 17th-18th, 2018 the CESCG held its fourth annual stem cell genomic CIRM retreat at Salk Institute. CIP1 has collected 289 blood samples in total and generated a valuable resource of 249 induced pluripotent stem cell lines. Whole genome sequencing from the first batch of 207 iPSCs has been completed and data analyzed. CIP1 has also differentiated 49 iPSCs into cardiomyocytes and treated them with various drugs followed by RNA-Seq. CIP2 has finished the collection of pancreas cells studied by patch-clamp cells and followed by single-cell RNA-seq. They have collected over 1,000 cells that passed quality control after sequencing, including over 300 cells from type-2 diabetes donors. Additional improvements have been made to the TCL-Seq method. The single-cell mRNA-seq pipeline has been cost reduced, and the throughput has been dramatically increased. In addition, a manuscript drafting on fetal pancreas is underway. All other CRP collaborators have made a significant progress in their projects. These research projects from the CIPs and CRPs will transform stem cell research in California and continue its preeminence in this area.
Reporting Period:
Year 5
This grant has enabled a plethora of activities pertaining to stem cell genomics in the state of California. The Stanford Administrative Core for the Center of Excellence in Stem Cell Genomics (CESCG) has been established and is responsible for overseeing joint center activities and the administration of center-initiated projects (CIP) 1 and 2, and several collaborative research projects (CRP). In the fifth year of the award the CESCG administration organized monthly conference calls to share research progress and coordinate activities across the center. On May 18th-19th, 2019 the CESCG held its fifth annual stem cell genomic CIRM retreat at Stanford University. CIP1 have completed the recruitment, reprogramming, and WGS of the diseased lines of our biobank. CIP1 has also differentiated a large number of iPSCs into cardiomyocytes and treated them with various drugs followed by RNA-Seq. CIP2 has focused on data analysis, making data public through the cell browser, manuscript drafting, and driving targeted chromatic ligation to automation and single-cell sensitivity. All other CRP collaborators have made a significant progress in their projects. These research projects from the CIPs and CRPs have led to more than 36 publications and several bioinformatics tools that will transform stem cell research in California and continue its preeminence in this area.
Reporting Period:
Year 6 NCE
This grant has enabled a plethora of activities pertaining to stem cell genomics in the state of California. The Stanford Administrative Core for the Center of Excellence in Stem Cell Genomics (CESCG) has been established and is responsible for overseeing joint center activities and the administration of center-initiated projects (CIP) 1 and 2, and several collaborative research projects (CRP). In the No-Cost Extension (NCE) period of the award, the CESCG administration organized monthly conference calls of CIP1 and coordinated activities of CRP projects that requested NCE. CIP1 completed the reprogramming of the biobank of 300 iPSC lines, generated the WGS of these lines, and identified candidate mutations for 30% of diseased lines. CIP1 also differentiated about half of the biobank into cardiomyocytes and treated them with various drugs followed by RNA-seq, and identified genes correlated with both disease and contractility. CIP2 completed their aims at the end of the last reporting period and did not require a NCE. All other CRP collaborators that requested a NCE have completed their sequencing projects. These research projects from the CIPs and CRPs have led to more than 40 publications and several bioinformatics tools that will transform stem cell research in California and continue its preeminence in this area.
Grant Application Details
Application Title:
Center of Excellence for Stem Cell Genomics
Public Abstract:
The Center of Excellence in Stem Cell Genomics will bring together investigators from seven major California research institutions to bridge two fields – genomics and pluripotent stem cell research. The projects will combine the strengths of the center team members, each of whom is a leader in one or both fields. The program directors have significant prior experience managing large-scale federally-funded genomics research programs, and have published many high impact papers on human stem cell genomics. The lead investigators for the center-initiated projects are expert in genomics, hESC and iPSC derivation and differentiation, and bioinformatics. They will be joined by leaders in stem cell biology, cancer, epigenetics and computational systems analysis. Projects 1-3 will use multi-level genomics approaches to study stem cell derivation and differentiation in heart, tumors and the nervous system, with implications for understanding disease processes in cancer, diabetes, and cardiac and mental health. Project 4 will develop novel tools for computational systems and network analysis of stem cell genome function. A state-of-the-art data management program is also proposed. This research program will lead the way toward development of the safe use of stem cells in regenerative medicine. Finally, Center resources will be made available to researchers throughout the State of California through a peer-reviewed collaborative research program.
Statement of Benefit to California:
Our Center of Excellence for Stem Cell Genomics will help California maintain its position at the cutting edge of Stem Cell research and greatly benefit California in many ways. First, diseases such as cardiovascular disease, cancer, neurological diseases, etc., pose a great financial burden to the State. Using advanced genomic technologies we will learn how stem cells change with growth and differentiation in culture and can best be handled for their safe use for therapy in humans. Second, through the collaborative research program, the center will provide genomics services to investigators throughout the State who are studying stem cells with a goal of understanding and treating specific diseases, thereby advancing treatments. Third, it will employ a large number of “high tech” individuals, thereby bringing high quality jobs to the state. Fourth, since many investigators in this center have experience in founding successful biotech companies it is likely to “spin off” new companies in this rapidly growing high tech field. Fifth, we believe that the iPS and information resources generated by this project will have significant value to science and industry and be valuable for the development of new therapies. Overall, the center activities will create a game-changing network effect for the state, propelling technology development, biological discovery and disease treatment in the field.
