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Updated: Jun 16, 2025
Single-cell Transcriptomic Analyses of Mouse Pancreatic Endocrine Cells
Published on: September 30, 2018
Integrating Spatial and Single-Nucleus Transcriptomic Data to Assess the Effects of Intrauterine Hyperglycemia on
Yu Deng1,2, Shuting Wan1,2, Zan Yuan3,4
1Department of Obstetrics and Gynecology, Peking University First Hospital, No. 8 Xishiku Street, Beijing, 100034, China.
Insights
Maternal diabetes impacts fetal pancreas development, causing cellular stress and altered cell communication. This study reveals key molecular changes in the developing fetal pancreas under these conditions.
Area of Science:
- Developmental Biology
- Endocrinology
- Genomics
Background:
- Maternal pregestational diabetes mellitus (PGDM) poses risks to fetal development.
- Specific effects of maternal PGDM on fetal pancreas cellular function and communication are not well understood.
Purpose of the Study:
- To investigate cellular responses and spatial alterations in the fetal pancreas under maternal PGDM.
- To elucidate molecular mechanisms of fetal pancreatic adaptation to maternal diabetes.
Main Methods:
- Single-nucleus RNA sequencing (snRNA-seq) to analyze cellular heterogeneity and gene expression.
- Spatial transcriptomics (ST) to map cellular changes within the pancreatic tissue.
- Analysis of fetal pancreas at embryonic days E16.5 and E18.5.
Main Results:
- Identified significant cellular heterogeneity and metabolic stress in fetal pancreatic acinar and beta cells.
- Observed decreased insulin secretion with compensatory upregulation of Pdx1, Nkx6.2, and Mafa.
- Detected substantial alterations in cell-cell communication and enhanced spatial enrichment in affected niches.
Conclusions:
- Maternal PGDM induces significant cellular and molecular changes in the developing fetal pancreas.
- Provides a spatiotemporal understanding of fetal pancreatic responses to maternal diabetes.
- Offers insights into mechanisms underlying adverse fetal outcomes in diabetic pregnancies.
Abstract:
Maternal pregestational diabetes mellitus (PGDM) can lead to adverse fetal outcomes, including lasting impacts on pancreatic development. However, the specific impacts of maternal PGDM on cellular functions and intercellular communication within the fetal pancreas remain poorly understood. Here, single-nucleus RNA sequencing and spatial transcriptomics (ST) are employed to investigate cellular responses and spatial changes in the fetal pancreas (E16.5 and E18.5) under maternal PGDM conditions. The findings reveal significant cellular heterogeneity among acinar and beta cells, along with pronounced metabolic stress responses. More importantly, decreased insulin secretion is observed and accompanied by the compensatory increase of Pdx1, Nkx6.2, and Mafa, and substantial alterations in cell-cell communication across multiple cell types. ST analysis further highlights enhanced spatial enrichment in cellular niches exposed to maternal PGDM. These findings provide valuable insights into the molecular mechanisms underlying fetal pancreatic response to maternal PGDM and offer a detailed spatiotemporal perspective on these processes.
