When
Where
ENR2, Room S225
Presenter Details
Abhinav Sur, Postdoctoral Fellow, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health
Seminar Information
During development, animals generate distinct cell populations with specific identities, functions, and morphologies. We mapped transcriptionally distinct populations across 489,686 cells from 62 stages during wild-type zebrafish embryogenesis and early larval development (3–120 hours post-fertilization). Using these data, we identified the limited catalog of gene expression programs reused across multiple tissues and their cell-type-specific adaptations. Focused clustering and transcriptional trajectory analyses of non-skeletal muscle and endoderm identified transcriptional profiles and candidate transcriptional regulators of understudied cell types and subpopulations, including the pneumatic duct, individual intestinal smooth muscle layers, spatially distinct pericyte subpopulations, and recently discovered best4+ cells. To enable additional discoveries, we make this comprehensive transcriptional atlas of early zebrafish development available through our website, Daniocell. Using developmental trajectory analysis, we predicted the progenitors of best4+ cells (secretory), signals (Notch) and transcription factors (TFs) important for their specification. Experimental validation via Notch inhibition led to best4+ cell loss and increased enteroendocrine cells (EECs), while Notch upregulation resulted in the opposite phenotype suggesting that best4+ cells share a common progenitor with EECs. We generated a secretory progenitor-specific knock-in line and followed these cells live to establish that best4+ cells arise from secretory progenitors. Live imaging of best4+ cells captured transient cellular projections in multiple directions, suggesting interactions with the gut lumen and other gut cells. To test the TF candidates, we generated stable whole gene deletions and profiled them via scRNAseq and staining, which identified TFs required for specification of best4+ cells and for regulating their regionalized gene expression. Complementary to mutants, we jointly profiled gene expression and chromatin accessibility of intestinal cells before, during, and after best4+ cell specification to begin more extensively predicting the developmental gene regulatory network of best4+ cells. Funding: ZIAHD008997 (JAF), 1K99HD115786 (AS).
Seminar Host
Dr. Ryan Gutenkunst (MCB)