Integrating single-cell imaging and RNA sequencing datasets links differentiation and morphogenetic dynamics of human pancreatic endocrine progenitors
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
Abstract
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.
Details
Original language | English |
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Pages (from-to) | 2292-2308.e6 |
Journal | Developmental cell |
Volume | 58 |
Issue number | 21 |
Publication status | Published - 6 Nov 2023 |
Peer-reviewed | Yes |
External IDs
PubMed | 37591246 |
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Keywords
Sustainable Development Goals
ASJC Scopus subject areas
Keywords
- diabetes, endocrine, human development, in vitro differentiation, live imaging, Neurogenin 3, pancreas, pancreatic progenitors, single-cell RNA sequencing, stem cells