Dr. Sneddon grew up in Brookline, Massachusetts and then attended Harvard University, where she earned her A.B. magna cum laude in Biochemical Sciences and performed her honors thesis research in Chemical Biology with Dr. Stuart Schreiber. She earned her Ph.D. in Biochemistry and genomics at Stanford University in the laboratory of Dr. Patrick O. Brown, and completed a post-doctoral fellowship in stem cell and cell replacement therapy for diabetes in the laboratory of Dr. Douglas Melton at Harvard University. Dr. Sneddon’s primary research goals are directed towards understanding pancreatic development, disease, and regeneration. Her laboratory has published an atlas of lineage dynamics of pancreatic development at single-cell resolution in the mouse, work that led to the discovery of a novel endocrine progenitor cell not previously described. More recently, her group has extended this work to human tissue to generate a multi-omic atlas of human fetal pancreatic development, identifying both novel human endocrine progenitor populations and lineage dynamics that are divergent from those in the mouse. In addition, her laboratory is modeling these novel insights about human beta cell specification in the dish, using the platform of human embryonic stem cell differentiation. In addition to Dr. Sneddon’s work in developmental biology, she has concomitantly retained a sharp focus on the generation of functional, mature stem cell-derived beta cells and their efficient transplantation to cure diabetes. In studying the role of the vascular niche in beta cell specification and maturation, for instance, her laboratory has found that recapitulation of key elements of the endogenous beta cell vascular niche in vitro leads to improved engraftment and function of stem cell-derived beta cells in vivo. In 2019, Dr. Sneddon was awarded the international Helmholtz Young Investigator in Diabetes (HelDi) prize, in recognition of outstanding achievements by a young scientist.
Interrogating human pancreas development for improved generation of stem cell-derived islets
Sean de la O1,2,3, Zhe Liu1,2,3, Han Sun4,6, Seth A Sharp4,6, Aaron D Tward3,5, Anna L Gloyn4,6, Julie Sneddon1,2,3.
1Cell & Tissue Biology, University of California, San Francisco, San Francisco, CA, United States; 2Diabetes Center, University of California, San Francisco, San Francisco, CA, United States; 3Eli & Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, United States; 4Pediatrics, Stanford University, Stanford, CA, United States; 5Otolaryngology - Head and Neck Surgery, University of California, San Francisco, San Francisco, CA, United States; 6Stanford Diabetes Research Center, Stanford University, Stanford, CA, United States
The critical cellular transitions that govern pancreas development in the human are largely unknown. Using a combination of single-cell RNA-sequencing, single-nucleus ATAC-sequencing, multiplexed RNA in situ hybridization and immunofluorescence validation in tissue, and functional validation in human pluripotent stem cell-derived beta cells, we have generated an extensive and validated multi-omic roadmap of human pancreatic development.
This map serves as a guidebook for human endocrine development, identifying novel intermediate progenitor states and lineage relationships, and characterizing cellular dynamics across developmental time. These results have critical implications for the field of regenerative medicine and for the implantation of human stem cell-derived beta cells as a treatment for diabetes. Our work shows that the current gold standard differentiation protocols are likely generating predominantly beta cell progenitors (rather than mature or even immature beta cells, as previously believed), in addition to a variety of cell states not well represented in the normal developing pancreas.
To improve protocols for differentiation of stem cell-derived beta cells, we need a roadmap of the critical factors and transitions in normal human development that we as a field are attempting to emulate. Our data indicate that the lineage trajectories taken by beta cells in human development demonstrate key differences from those in the better characterized mouse. We also identify key transcription factors that are aberrantly expressed or missing in stem cell-derived beta cells versus endogenous developing beta cells. Refinement of our differentiation protocols based upon this human-specific developmental roadmap will be critical in understanding what our goals should be with regards to purity and identity of stem cell-derived beta cells and their progenitors.
Grant from NIH/NIDDK (R01DK118421) to J.B.S.. Grant from JDRF (2-SRA-2019-773-S-B) to J.B.S.. Kraft Family Fellowship to the UCSF Diabetes Center for S.D.. UCSF Discovery Fellows Program for S.D.. NIH NIGMS IMSD Grant #R25GM056847-23 for S.D.. NIH/NIDDK diversity supplement R01DK118421-02S1 for S.D.. Jeffrey G. Klein Family Diabetes Fellowship to the UCSF Diabetes Center (for Z.L.). Grants from NIH/NIDDK (U01-DK105535; U01-DK085545, UM1DK126185) to A.L.G.. Grant from NIH/NIDDK NIDDK to the Stanford Diabetes Research Center (award P30DK116074) and A.L.G.. Grant from Wellcome (200837) to A.L.G.. Gregory Szot, UCSF Islet Production Core.
Insights from Islet Biology for Making Stem Cell-Derived Islets
