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A 3D system to model human pancreas development and its reference single-cell transcriptome atlas identify signaling pathways required for progenitor expansion.

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

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Citation

Gonçalves, C. A. C., Larsen, M., Jung, S., Stratmann, J., Nakamura, A., Leuschner, M., et al. (2021). A 3D system to model human pancreas development and its reference single-cell transcriptome atlas identify signaling pathways required for progenitor expansion. Nature communications, 12(1): 3144. doi:10.1038/s41467-021-23295-6.


Cite as: https://hdl.handle.net/21.11116/0000-0008-DA74-0
Abstract
Human organogenesis remains relatively unexplored for ethical and practical reasons. Here, we report the establishment of a single-cell transcriptome atlas of the human fetal pancreas between 7 and 10 post-conceptional weeks of development. To interrogate cell-cell interactions, we describe InterCom, an R-Package we developed for identifying receptor-ligand pairs and their downstream effects. We further report the establishment of a human pancreas culture system starting from fetal tissue or human pluripotent stem cells, enabling the long-term maintenance of pancreas progenitors in a minimal, defined medium in three-dimensions. Benchmarking the cells produced in 2-dimensions and those expanded in 3-dimensions to fetal tissue identifies that progenitors expanded in 3-dimensions are transcriptionally closer to the fetal pancreas. We further demonstrate the potential of this system as a screening platform and identify the importance of the EGF and FGF pathways controlling human pancreas progenitor expansion.