Deciphering early human pancreas development at the single-cell level

被引:0
作者
Zhuo Ma
Xiaofei Zhang
Wen Zhong
Hongyan Yi
Xiaowei Chen
Yinsuo Zhao
Yanlin Ma
Eli Song
Tao Xu
机构
[1] Chinese Academy of Sciences,National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics
[2] University of Chinese Academy of Sciences,College of Life Sciences
[3] Huazhong University of Science and Technology,Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology
[4] The First Affiliated Hospital of Hainan Medical University,Hainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research, Key Laboratory of Reproductive Health Diseases Research and Translation (Hainan Medical University), Ministry
[5] Hainan Medical University,Science for Life Laboratory, Department of Biomedical and Clinical Sciences (BKV)
[6] Linköping University,Department of Neuroscience
[7] Karolinska Institutet,Center for High Throughput Sequencing, Core Facility for Protein Research, Key Laboratory of RNA Biology, Institute of Biophysics
[8] Chinese Academy of Sciences,Medical Science and Technology Innovation Center
[9] Guangzhou Laboratory,undefined
[10] Central Hospital Affiliated to Shandong First Medical University,undefined
[11] Shandong First Medical University & Shandong Academy of Medical Sciences,undefined
来源
Nature Communications | / 14卷
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摘要
Understanding pancreas development can provide clues for better treatments of pancreatic diseases. However, the molecular heterogeneity and developmental trajectory of the early human pancreas are poorly explored. Here, we performed large-scale single-cell RNA sequencing and single-cell assay for transposase accessible chromatin sequencing of human embryonic pancreas tissue obtained from first-trimester embryos. We unraveled the molecular heterogeneity, developmental trajectories and regulatory networks of the major cell types. The results reveal that dorsal pancreatic multipotent cells in humans exhibit different gene expression patterns than ventral multipotent cells. Pancreato-biliary progenitors that generate ventral multipotent cells in humans were identified. Notch and MAPK signals from mesenchymal cells regulate the differentiation of multipotent cells into trunk and duct cells. Notably, we identified endocrine progenitor subclusters with different differentiation potentials. Although the developmental trajectories are largely conserved between humans and mice, some distinct gene expression patterns have also been identified. Overall, we provide a comprehensive landscape of early human pancreas development to understand its lineage transitions and molecular complexity.
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