Table_1_Gene Signatures of NEUROGENIN3+ Endocrine Progenitor Cells in the Human Pancreas.docx
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.
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References
- https://doi.org//10.1073/pnas.0308647100
- https://doi.org//10.1038/23716
- https://doi.org//10.1242/dev.127.16.3533
- https://doi.org//10.1038/nature07314
- https://doi.org//10.1002/dvdy.21740
- https://doi.org//10.1242/dev.129.10.2447
- https://doi.org//10.1016/j.cell.2007.12.015
- https://doi.org//10.1242/dev.090159
- https://doi.org//10.1038/cddis.2013.52
- https://doi.org//10.1242/dev.039214
- https://doi.org//10.1016/j.devcel.2018.11.048
- https://doi.org//10.1056/NEJMoa054288
- https://doi.org//10.2337/db10-1008
- https://doi.org//10.1210/jc.2011-0029
- https://doi.org//10.1111/pedi.12576
- https://doi.org//10.2337/db14-1412
- https://doi.org//10.1038/nbt1259
- https://doi.org//10.1038/nbt.3033
- https://doi.org//10.1016/j.cell.2014.09.040
- https://doi.org//10.1007/s00125-007-0880-0
- https://doi.org//10.1007/s00125-008-1006-z
- https://doi.org//10.2337/db12-1479
- https://doi.org//10.1371/journal.pone.0133862
- https://doi.org//10.1111/joa.12418
- https://doi.org//10.1016/j.celrep.2018.02.006
- https://doi.org//10.1111/dom.12718
- https://doi.org//10.2337/db16-0405
- https://doi.org//10.1016/j.cmet.2016.08.020
- https://doi.org//10.1016/j.cell.2017.09.004
- https://doi.org//10.1016/j.molmet.2020.101057
- https://doi.org//10.1093/bioinformatics/bts635
- https://doi.org//10.1038/nbt.1754
- https://doi.org//10.1101/576827
- https://doi.org//10.1093/gigascience/giy083
- https://doi.org//10.1093/nar/gkv007
- https://doi.org//10.1093/nar/gky1131
- https://doi.org//10.1242/dev.165480
- https://doi.org//10.1016/j.stemcr.2018.11.008
- https://doi.org//10.1016/j.cmet.2019.01.003
- https://doi.org//10.1186/gb-2006-7-10-r100
- https://doi.org//10.1126/science.aal3321
- https://doi.org//10.1016/j.ydbio.2005.07.021
- https://doi.org//10.2337/db15-0713
- https://doi.org//10.3390/biom8040161
- https://doi.org//10.3233/JAD-2011-102115
- https://doi.org//10.1016/0014-5793%2889%2980113-9
- https://doi.org//10.1073/pnas.0308647100
- https://doi.org//10.1038/onc.2010.258
- https://doi.org//10.1172/JCI33768
- https://doi.org//10.1074/jbc.m501026200
- https://doi.org//10.1016/j.ajhg.2009.01.011
- https://doi.org//10.1095/biolreprod.112.102905
- https://doi.org//10.1016/S0092-8674%2800%2981921-2
- https://doi.org//10.1158/1078-0432.CCR-10-3431
- https://doi.org//10.1128/MCB.20.9.3292-3307.2000
- https://doi.org//10.1074/jbc.M213196200
- https://doi.org//10.1038/387406a0
- https://doi.org//10.1242/dev.041673
- https://doi.org//10.1074/jbc.M112.388173
- https://doi.org//10.1016/j.ydbio.2006.06.030
- https://doi.org//10.1128/MCB.18.9.5109
- https://doi.org//10.1002/dvdy.24182
- https://doi.org//10.1016/j.celrep.2018.11.078
- https://doi.org//10.3389/fgene.2017.00013
- https://doi.org//10.1016/j.cels.2016.08.011
- https://doi.org//10.1016/j.stem.2016.05.010
- https://doi.org//10.15252/embr.201540946
- https://doi.org//10.1016/j.cels.2016.09.002
- https://doi.org//10.1016/j.cmet.2016.08.018
- https://doi.org//10.1101/gr.212720.116
- https://doi.org//10.2337/db18-0365
- https://doi.org//10.1053/j.gastro.2020.11.010
- https://doi.org//10.1371/journal.pone.0052026
- https://doi.org//10.1038/s41467-018-06176-3
- https://doi.org//10.1101/gad.284729.116
- https://doi.org//10.1242/dev.163162
- https://doi.org//10.1038/s41467-018-05740-1