run_metadata: 312

This data as json

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312	ERR977399	ERX1054382	ERS805483	ERP011343	PRJEB10137	RNAseq from mature ductal cells from nkx6.1:GFP zebrafish lines	ena-STUDY-GIGA-R, University of Liege-05-08-2015-09:45:38:475-48	Other	Background: In contrast to mammals the zebrafish has the remarkable capacity to regenerate very efficiently its pancreatic beta cells. Understanding the mechanisms of regeneration in zebrafish and the differences with mammals will be fundamental to discovering molecules able to stimulate the regeneration process in mammals. To identify the pancreatic cells able to give rise to new beta cells in zebrafish we generated new transgenic lines allowing the tracing of multipotent pancreatic progenitors and endocrine precursors. Results: Using novel bacterial artificial chromosome transgenic nkx6.1 and ascl1b reporter lines we established that nkx6.1 positive cells give rise to all the pancreatic cell types and ascl1b positive cells give rise to all the endocrine cell types in the zebrafish embryo. These two genes are initially co expressed in the pancreatic primordium and their domains segregate not as a result of mutual repression but through the opposite effects of Notch signaling maintaining nkx6.1 expression while repressing ascl1b in progenitors. In adult zebrafish nkx6.1 expression persists exclusively in the ductal tree at the tip of which its expression coincides with Notch active signaling in centroacinar/terminal end duct cells. Tracing these cells reveals that they are able to differentiate into other ductal cells and into Insulin expressing cells in normal – non diabetic – animals. This capacity of ductal cells to generate endocrine cells is supported by the detection of ascl1b in the nkx6.1:GFP ductal cell transcriptome. This transcriptome also reveals besides actors of the Notch and Wnt pathways several novel markers such as id2a. Finally we show that beta cell ablation in adult zebrafish triggers proliferation of ductal cells and their differentiation into Insulin expressing cells. Conclusions: We have shown that in the zebrafish embryo nkx6.1+ cells are bona fide multipotent pancreatic progenitors while ascl1b+ cells represent committed endocrine precursors. In contrast to mouse pancreatic progenitor markers nkx6.1 and pdx1 continue to be expressed in adult ductal cells a subset of which we show are still able to proliferate and undergo ductal and endocrine differentiation providing the first robust evidence of the existence of pancreatic progenitor/stem cells in adult zebrafish. Our findings support the hypothesis that nkx6.1+ pancreatic progenitors contribute to beta cell regeneration. Further characterization of these cells will open up new perspectives for anti diabetic therapies.				Ductal cells R3	SAMEA3498334	GIGA-R, University of Liege	ENA first public:2015 08 17\|ENA last update:2015 08 05\|External Id:SAMEA3498334\|INSDC center alias:GIGA R University of Liege\|INSDC center name:GIGA R University of Liege\|INSDC first public:2015 08 17T17:01:08Z\|INSDC last update:2015 08 05T10:19:01Z\|INSDC status:public\|Submitter Id:3\|cell type:Pancreatic Ductal cells\|collected by:Isabelle Manfroid and David Bergeman\|common name:zebrafish\|dev stage:Adult\|isolate:Tgnkx6.1:GPF\|lab host:ZDDM\|sample name:3\|strain:Tgnkx6.1:GPF									Illumina HiSeq 2000 paired end sequencing	ena EXPERIMENT GIGA R University of Liege 05 08 2015 10:18:44:269 3	unspecified	1	nextera XT		RNA-Seq	TRANSCRIPTOMIC	Oligo-dT	PAIRED	ILLUMINA	Illumina HiSeq 2000		ERP011343	Illumina HiSeq 2000 paired end sequencing	ENA FIRST PUBLIC:2015 08 17\|ENA LAST UPDATE:2018 11 16	NGS14-B703_nkx2_TCCTGAGC_L003_R1_001.fastq.gz NGS14-B703_nkx2_TCCTGAGC_L003_R2_001.fastq.gz	fastq fastq	14253683247.0	70913847.0	ena RUN GIGA R University of Liege 05 08 2015 10:18:44:269 3	0:101 1:100	A:3767730088;C:2759135663;G:2772107550;T:3905748607;N:1048961339	101	100			3767730088	2759135663	2772107550	3905748607	1048961339	ERX1054382	ERS805483	ERA463457	GIGA-R, University of Liege\|European Nucleotide Archive	GIGA-R, University of Liege	2	0.74612	0.7459	0.10937	0.11122	0.81704	0.81913	0.54841	0.53764	101	100	B	B	biological fallback assumption	illumina	hiseq_era	unknown	poly_a	nextera	bulk	unknown	unknown		Belgium	2015-08-05	Adult	Adult	Undetermined	Undetermined