A Single-Cell Transcriptome Atlas of the Human Pancreas

被引:810
作者
Muraro, Mauro J. [1 ,2 ]
Dharmadhikari, Gitanjali [1 ,2 ]
Gruen, Dominic [1 ,2 ,3 ]
Groen, Nathalie [6 ]
Dielen, Tim [1 ,2 ]
Jansen, Erik [1 ,2 ]
van Gurp, Leon [1 ,2 ]
Engelse, Marten A. [4 ,5 ]
Carlotti, Francoise [6 ]
de Koning, Eelco J. P. [1 ,2 ,4 ,5 ]
van Oudenaarden, Alexander [1 ,2 ]
机构
[1] KNAW Royal Netherlands Acad Arts & Sci, Hubrecht Inst, NL-3584 CX Utrecht, Netherlands
[2] Univ Med Ctr Utrecht, Canc Genom Netherlands, NL-3584 CX Utrecht, Netherlands
[3] Max Planck Inst Immunobiol & Epigenet, D-79108 Freiburg, Germany
[4] Leiden Univ, Nephrol Sect, Dept Med, Med Ctr, NL-2333 ZA Leiden, Netherlands
[5] Leiden Univ, Endocrinol Sect, Dept Med, Med Ctr, NL-2333 ZA Leiden, Netherlands
[6] Leiden Univ, Med Ctr, Dept Internal Med, NL-2333 ZA Leiden, Netherlands
关键词
RNA-SEQ; INSULIN-SECRETION; GENE-EXPRESSION; ISLET TRANSCRIPTOME; BETA; GLUCOSE; DIFFERENTIATION; ALPHA; HETEROGENEITY; LANDSCAPE;
D O I
10.1016/j.cels.2016.09.002
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
To understand organ function, it is important to have an inventory of its cell types and of their corresponding marker genes. This is a particularly challenging task for human tissues like the pancreas, because reliable markers are limited. Hence, transcriptome-wide studies are typically done on pooled islets of Langerhans, obscuring contributions from rare cell types and of potential subpopulations. To overcome this challenge, we developed an automated platform that uses FACS, robotics, and the CEL-Seq2 protocol to obtain the transcriptomes of thousands of single pancreatic cells from deceased organ donors, allowing in silico purification of all main pancreatic cell types. We identify cell type-specific transcription factors and a subpopulation of REG3A-positive acinar cells. We also show that CD24 and TM4SF4 expression can be used to sort live alpha and beta cells with high purity. This resource will be useful for developing a deeper understanding of pancreatic biology and pathophysiology of diabetes mellitus.
引用
收藏
页码:385 / +
页数:13
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