CDB Seminar - Dr Margarete Diaz Cuadros, Harvard Medical School
'Regulation of species-specific developmental rates by redox metabolism'
CDB Seminar - Dr Margarete Diaz Cuadros, Harvard Medical School
30 Jan 2025, 13:00 – 14:00
Please join us for a CDB Seminar by Dr Margarete Diaz Cuadros of the Massachusetts General Hospital and Harvard Medical School.
Zoom at: https://ucl.zoom.us/j/94880674613
Talk abstract: Developmental processes during embryogenesis are conserved across mammals, yet the rate of development varies significantly between species. While embryogenesis in mice is completed in 15 days, human development spans 56 days. Understanding the molecular mechanisms underlying these differences is critical for improving the differentiation of human induced pluripotent stem cells (iPSCs) for disease modeling and regenerative therapies. We recently established an in vitro system that recapitulates the 2-3 fold difference in developmental rate between mouse and human embryos. This model relies on the differentiation of mouse and human pluripotent stem cells to presomitic mesoderm (PSM), a cell type that harbors a molecular oscillator known as the segmentation clock. This clock provides a high-resolution, quantitative proxy for developmental speed. Using this system, we previously found that the cytosolic NAD+/NADH ratio plays a key role in regulating developmental rates, with higher NAD+/NADH ratios associated with faster development. This redox balance is modulated by electron shuttling systems, notably the glycerol-3-phosphate (G3P) and malate-aspartate (MA) shuttles. We have found that the G3P shuttle is active in mouse PSM cells but not in human PSM cells due to species-specific expression patterns of G3P shuttle enzymes. Exogenously expressing G3P shuttle enzymes in human cells increases flux through this shuttle, raises the NAD+/NADH ratio, and accelerates the segmentation clock. By elucidating the molecular mechanisms governing developmental timing, this research provides critical insights into species-specific differences and enhance the utility of iPSCs for therapeutic applications.
Suggested references: Diaz-Cuadros M, Miettinen TP, Skinner OS, Sheedy D, Díaz-García CM, Gapon S, Hubaud A, Yellen G, Manalis SR, Oldham WM, Pourquié O. Metabolic regulation of species-specific developmental rates. Nature. 2023 Jan;613(7944):550-557. doi: 10.1038/s41586-022-05574-4. Epub 2023 Jan 4. Erratum in: Nature. 2023 Apr;616(7956):E4. doi: 10.1038/s41586-023-05924-w. PMID: 36599986; PMCID: PMC9944513.
Host: Alessandro Mongera
Massachusetts General Hospital and Harvard Medical School
Margarete is a Junior Fellow in the Department of Molecular Biology at Massachusetts General Hospital. She earned her Bachelor’s degree in biochemistry at Columbia University (2014) and was named class valedictorian. As an undergraduate, she worked in Dr. Martin Chalfie's laboratory investigating neuronal subtype differentiation in the nematode Caenorhabditis elegans. She later completed her PhD under the supervision of Dr. Olivier Pourquie at Harvard Medical School (2022). Her graduate research focused on the development of in vitro systems for the recapitulation of the mammalian segmentation clock based on pluripotent stem cells. Through a special fellow’s program, Margarete launched her independent research group directly after completion of her PhD. The Diaz Cuadros laboratory focuses on understanding the molecular and genetic basis of species-specific developmental rates by combining in vitro stem cell work with in vivo studies in C. elegans. Born and raised in Lima, Peru, Margarete enjoys cooking, baking, and looking after her vegetable garden. She was co-director of the Research Experience for Peruvian Undergraduates program for four years and currently serves on the Committee for the Advancement of Women in Science in Peru.