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

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

39 Citationer (Scopus)

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.

OriginalsprogEngelsk
Artikelnummer3144
TidsskriftNature Communications
Vol/bind12
Udgave nummer1
Sider (fra-til)1-17
Antal sider17
DOI
StatusUdgivet - 25 maj 2021

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