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Integrating single-cell imaging and RNA sequencing datasets links differentiation and morphogenetic dynamics of human pancreatic endocrine progenitors.

MPG-Autoren
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Beydag-Tasöz,  Belin Selcen
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

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Luppino,  Federica
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

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Kim,  Yung Hae
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

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Zechner,  Christoph
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

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Grapin-Botton,  Anne
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

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Zitation

Beydag-Tasöz, B. S., D'Costa, J. V., Hersemann, L., Lee, B. H., Luppino, F., Kim, Y. H., et al. (2023). Integrating single-cell imaging and RNA sequencing datasets links differentiation and morphogenetic dynamics of human pancreatic endocrine progenitors. Developmental cell, 58(21), 2292-2308. doi:10.1016/j.devcel.2023.07.019.


Zitierlink: https://hdl.handle.net/21.11116/0000-000E-AB00-1
Zusammenfassung
Basic helix-loop-helix genes, particularly proneural genes, are well-described triggers of cell differentiation, yet information on their dynamics is limited, notably in human development. Here, we focus on Neurogenin 3 (NEUROG3), which is crucial for pancreatic endocrine lineage initiation. By monitoring both NEUROG3 gene expression and protein in single cells using a knockin dual reporter in 2D and 3D models of human pancreas development, we show an approximately 2-fold slower expression of human NEUROG3 than that of the mouse. We observe heterogeneous peak levels of NEUROG3 expression and reveal through long-term live imaging that both low and high NEUROG3 peak levels can trigger differentiation into hormone-expressing cells. Based on fluorescence intensity, we statistically integrate single-cell transcriptome with dynamic behaviors of live cells and propose a data-mapping methodology applicable to other contexts. Using this methodology, we identify a role for KLK12 in motility at the onset of NEUROG3 expression.