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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)
Verlagsversion DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter 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
Zeitschrift Developmental Cell
Quellenangaben Band: 58, Heft: 21, Seiten: 2292-2308.e6 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Pancreatic Islet Research (IPI)
Förderungen Copenhagen Bioscience PhD program by the Novo Nordisk Fonden
Novo Nordisk Foundation