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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

ISSN (print) / ISBN 1534-5807

e-ISSN 1878-1551

Journal Developmental Cell

Quellenangaben Volume: 58, Issue: 21, Pages: 2292-2308.e6

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)

Grants Copenhagen Bioscience PhD program by the Novo Nordisk Fonden
Novo Nordisk Foundation