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Hvidovre Hospital - en del af Københavns Universitetshospital

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.

TidsskriftNature Communications
Udgave nummer1
StatusUdgivet - 25 maj 2021

Bibliografisk note

Funding Information:
We are grateful to Henrik Semb for the HuES4 PDX1-eGFP cell line. We thank the DanStem Genomics Platform, notably Magali Michaut and Helen McNeil, as well as Michaela Rothova for setting up MARS-Seq. We are also grateful to the Stem Cell Culture, Flow Cytometry, and Imaging Facilities and staff at DanStem and MPI-CBG for training, technical expertise, support, and the use of instruments. Data processing and analysis from the Genomics Platform were performed using the DeiC National Life Science Supercomputer at DTU ( We thank Josh Brickman for his comments on the manuscript. The Novo Nordisk Foundation Center for Stem Cell Biology is supported by a Novo Nordisk Foundation grant number NNF17CC0027852. The project was supported by grants 7016-00045B from Det Frie Forskningsråd and DNRF 116 from the Danish National Research Foundation to A.G.B.

ID: 65786195