Gene Signatures of NEUROGENIN3+ Endocrine Progenitor Cells in the Human Pancreas
- Resource Type
- article
- Authors
- Hyo Jeong Yong; Gengqiang Xie; Chengyang Liu; Wei Wang; Ali Naji; Jerome Irianto; Yue J. Wang
- Source
- Frontiers in Endocrinology, Vol 12 (2021)
- Subject
- NEUROG3
endocrine progenitor
epsilon cells
human pancreas
single-cell RNA-seq
data integration
Diseases of the endocrine glands. Clinical endocrinology
RC648-665
- Language
- English
- ISSN
- 1664-2392
NEUROGENIN3+ (NEUROG3+) cells are considered to be pancreatic endocrine progenitors. Our current knowledge on the molecular program of NEUROG3+ cells in humans is largely extrapolated from studies in mice. We hypothesized that single-cell RNA-seq enables in-depth exploration of the rare NEUROG3+ cells directly in humans. We aligned four large single-cell RNA-seq datasets from postnatal human pancreas. Our integrated analysis revealed 10 NEUROG3+ epithelial cells from a total of 11,174 pancreatic cells. Noticeably, human NEUROG3+ cells clustered with mature pancreatic cells and epsilon cells displayed the highest frequency of NEUROG3 positivity. We confirmed the co-expression of NEUROG3 with endocrine markers and the high percentage of NEUROG3+ cells among epsilon cells at the protein level based on immunostaining on pancreatic tissue sections. We further identified unique genetic signatures of the NEUROG3+ cells. Regulatory network inference revealed novel transcription factors including Prospero homeobox protein 1 (PROX1) may act jointly with NEUROG3. As NEUROG3 plays a central role in endocrine differentiation, knowledge gained from our study will accelerate the development of beta cell regeneration therapies to treat diabetes.