A 3D system to model human pancreas development and its reference single-cell transcriptome atlas identify signaling pathways required for progenitor expansion
| Autor: | Yung Hae Kim, Anne Grapin-Botton, Rashmiparvathi Keshara, Signe Perlman, Sascha Jung, Antonio del Sol, Michael Larsen, Carla A C Gonçalves, Akiko Nakamura, Kristine J. Hare, Lene Lundvall, Lena Hersemann, Johannes Stratmann, Ido Amit, Lea Langhoff Thuesen, Anne Jørgensen, Marit Leuschner |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Organogenesis Cellular differentiation Cell Culture Techniques Datasets as Topic General Physics and Astronomy Cell Communication Fibroblast growth factor Tissue Culture Techniques Transcriptome Mice 0302 clinical medicine RNA-Seq RNA-SEQ Induced pluripotent stem cell ORGANOGENESIS Multidisciplinary Gene Expression Regulation Developmental Cell Differentiation Cell biology DIFFERENTIATION medicine.anatomical_structure Aborted Fetus Single-Cell Analysis Pancreas Signal Transduction Pluripotent Stem Cells EXPRESSION Cell signaling TISSUES Science Stem-cell differentiation Biology Article General Biochemistry Genetics and Molecular Biology Cell Line 03 medical and health sciences BETA-CELLS Spheroids Cellular REVEALS medicine Animals Humans Progenitor cell Progenitor Epidermal Growth Factor IN-VITRO General Chemistry Embryo Mammalian DYSFUNCTION Fibroblast Growth Factors 030104 developmental biology 030217 neurology & neurosurgery GENERATION |
| Zdroj: | Goncalves, C A, Larsen, M, Jung, S, Stratmann, J, Nakamura, A, Leuschner, M, Hersemann, L, Keshara, R, Perlman, S, Lundvall, L, Thuesen, L L, Hare, K J, Amit, I, Jørgensen, A, Kim, Y H, del Sol, A & Grapin-Botton, A 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, vol. 12, 3144 . https://doi.org/10.1038/s41467-021-23295-6 Nature Communications Nature Communications, Vol 12, Iss 1, Pp 1-17 (2021) |
| DOI: | 10.21203/rs.3.pex-1430/v1 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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