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Hvidovre Hospital - a part of Copenhagen University Hospital
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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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  • Carla A Gonçalves
  • Michael Larsen
  • Sascha Jung
  • Johannes Stratmann
  • Akiko Nakamura
  • Marit Leuschner
  • Lena Hersemann
  • Rashmiparvathi Keshara
  • Signe Perlman
  • Lene Lundvall
  • Lea Langhoff Thuesen
  • Kristine Juul Hare
  • Ido Amit
  • Anne Jørgensen
  • Yung Hae Kim
  • Antonio Del Sol
  • Anne Grapin-Botton
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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.

Original languageEnglish
Article number3144
JournalNature Communications
Volume12
Issue number1
DOIs
Publication statusPublished - 25 May 2021

Bibliographical note

Publisher Copyright:
© 2021, The Author(s).

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

ID: 65786195