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Beydag-Tasöz, B.S.* ; D'Costa, J.V.* ; Hersemann, L.* ; Lee, B.H.* ; Luppino, F.* ; Kim, Y.H.* ; Zechner, C.* ; Grapin-Botton, A.

Integrating single-cell imaging and RNA sequencing datasets links differentiation and morphogenetic dynamics of human pancreatic endocrine progenitors.

Dev. Cell 58, 2292-2308.e6 (2023)
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Basic helix-loop-helix genes, particularly proneural genes, are well-described triggers of cell differentiation, yet information on their dynamics is limited, notably in human development. Here, we focus on Neurogenin 3 (NEUROG3), which is crucial for pancreatic endocrine lineage initiation. By monitoring both NEUROG3 gene expression and protein in single cells using a knockin dual reporter in 2D and 3D models of human pancreas development, we show an approximately 2-fold slower expression of human NEUROG3 than that of the mouse. We observe heterogeneous peak levels of NEUROG3 expression and reveal through long-term live imaging that both low and high NEUROG3 peak levels can trigger differentiation into hormone-expressing cells. Based on fluorescence intensity, we statistically integrate single-cell transcriptome with dynamic behaviors of live cells and propose a data-mapping methodology applicable to other contexts. Using this methodology, we identify a role for KLK12 in motility at the onset of NEUROG3 expression.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Neurogenin 3 ; Diabetes ; Endocrine ; Human Development ; In vitro Differentiation ; Live Imaging ; Pancreas ; Pancreatic Progenitors ; Single-cell Rna Sequencing ; Stem Cells; In-vitro; Neurogenin3; Expression; Reveals; Phosphorylation; Generation; Cycle; Reads; Mouse; Fate
Language english
Publication Year 2023
HGF-reported in Year 2023
ISSN (print) / ISBN 1534-5807
e-ISSN 1878-1551
Journal Developmental Cell
Quellenangaben Volume: 58, Issue: 21, Pages: 2292-2308.e6 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Reviewing status Peer reviewed
Institute(s) Institute of Pancreatic Islet Research (IPI)
POF-Topic(s) 90000 - German Center for Diabetes Research
PSP Element(s) A-502600-001
Grants Copenhagen Bioscience PhD program by the Novo Nordisk Fonden
Novo Nordisk Foundation
DOI 10.1016/j.devcel.2023.07.019
WOS ID 001109324300001
Scopus ID 85170289335
PubMed ID 37591246
Erfassungsdatum 2023-10-06
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