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- Title
A 3D system to model human pancreas development and its reference single-cell transcriptome atlas identify signaling pathways required for progenitor expansion.
- Authors
Gonçalves, Carla A.; Larsen, Michael; Jung, Sascha; Stratmann, Johannes; Nakamura, Akiko; Leuschner, Marit; Hersemann, Lena; Keshara, Rashmiparvathi; Perlman, Signe; Lundvall, Lene; Thuesen, Lea Langhoff; Hare, Kristine Juul; Amit, Ido; Jørgensen, Anne; Kim, Yung Hae; del Sol, Antonio; Grapin-Botton, Anne
- 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. From single-cell transcriptome analyses to defining culture media for spheroids, the authors provide a census of information to understand the development of human pancreatic progenitors. This approach identifies signalling pathways (EGF and FGF) regulating progenitor proliferation.
- Subjects
PANCREAS; PLURIPOTENT stem cells; FETAL tissues; HUMAN stem cells; CELL communication; PRACTICAL reason
- Publication
Nature Communications, 2021, Vol 12, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-021-23295-6