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Series GSE139218 Query DataSets for GSE139218
Status Public on Dec 24, 2019
Title Single-cell analysis uncovers that metabolic reprogramming is essential for cardiomyocyte proliferation in the regenerating heart.
Organism Danio rerio
Experiment type Expression profiling by high throughput sequencing
Summary While the heart regenerates poorly in mammals, efficient heart regeneration occurs in certain amphibian and fish species. Zebrafish has been used extensively to study heart regeneration, resulting in a model in which preexisting cardiomyocytes dedifferentiate and reinitiate proliferation to replace the lost myocardium. However, there is limited knowledge about the cellular processes that occur in this rare population of proliferating cardiomyocytes during heart regeneration. To identify such processes, we generated a transgenic line based on nppa expression that marks proliferating cardiomyocytes located at the wound border zone. Next we have used a single-cell RNA-sequencing approach in the regenerating adult zebrafish heart and we uncovered that proliferating border zone cardiomyocytes have very distinct transcriptomes compared to the non-proliferating remote cardiomyocytes and that they resemble embryonic cardiomyocytes. Moreover, these cells have reduced expression of mitochondrial genes and reduced mitochondrial oxidative phosphorylation activity, while glycolysis gene expression and glucose uptake are increased, indicative for metabolic reprogramming. Mechanistically, this metabolic reprogramming is induced by Nrg1/Erbb2 signaling and this mechanism is conserved in murine hearts.  Furthermore, pharmacological inhibition of glycolysis impairs cardiomyocyte proliferation of both zebrafish and murine cardiomyocytes. Together these results reveal a conserved mechanism in which cardiomyocytes undergo metabolic reprogramming, which is essential for cardiomyocyte proliferation and heart regeneration and could ultimately help to develop novel methods to promote mammalian heart repair.
 
Overall design Tg(nppa:mCitrine) positive cells (n=576) were collected from 13 cryoinjured hearts. As an internal control, also nppa negative cells were sorted. (n=192). In addition Tg(myl7:GFP) positive cells (n=768) were sorted from 2dpf embryos. All cells were sent for single cell RNA sequencing.
 
Contributor(s) Honkoop H, de Bakker DE, Aharonov A, Kruse F, Shakked A, Nguyen PD, de Heus C, Garric L, Muraro MJ, Shoffner A, Tessadori F, Peterson JC, Noort W, Bertozzi A, Weidinger G, Posthuma G, Grün D, van der Laarse WJ, Klumperman J, Jaspers RT, Poss KD, van Oudenaarden A, Tzahor E, Bakkers J
Citation(s) 31868166
Submission date Oct 21, 2019
Last update date Feb 10, 2020
Contact name Hessel Honkoop
E-mail(s) h.honkoop@hubrecht.eu
Organization name Hubrecht Institute
Lab Bakkers
Street address Uppsalalaan 8
City Utrecht
State/province Zuid-Holland
ZIP/Postal code 3584CT
Country Netherlands
 
Platforms (1)
GPL20828 Illumina NextSeq 500 (Danio rerio)
Samples (4)
GSM4134186 FK1
GSM4134187 FK2
GSM4134188 LG-A
Relations
BioProject PRJNA578764
SRA SRP226527

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Supplementary file Size Download File type/resource
GSE139218_RAW.tar 3.7 Mb (http)(custom) TAR (of CSV, TSV)
GSE139218_cel-seq2_barcodes.csv.gz 2.1 Kb (ftp)(http) CSV
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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