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| Status |
Public on Nov 30, 2018 |
| Title |
Efferocytosis induces a novel SLC program to promote glucose uptake and lactate release |
| Organism |
Cricetulus griseus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
On a daily basis, we turnover billions of apoptotic cells that are removed by professional and non-professional phagocytes1-10. While characterizing the transcriptional program of phagocytes, we discovered a novel solute carrier family (SLC) gene signature (33 SLC members) that is specifically modified during engulfment of apoptotic cells (efferocytosis) but not during antibody-mediated phagocytosis. When we assessed the functional relevance of these SLCs, we noted robust induction of an aerobic glycolysis program in engulfing phagocytes, initiated by SLC2A1-mediated glucose uptake, and suppression of oxidative phosphorylation program. Interestingly, the different steps of phagocytosis10,11, i.e. smell (‘find-me’ signals / sensing factors released by apoptotic cells), taste (phagocyte- apoptotic cell contact), and ingestion (corpse internalization), activated different molecules to promote this glycolytic process. Further, lactate, a natural by-product of aerobic glycolysis12,13, was released from engulfing phagocytes via SLC16A1, an SLC member activated after corpse uptake. While glycolysis within phagocytes contributed to actin polymerization and the continued uptake of corpses, the lactate released via SLC16A1 influenced the establishment of an anti-inflammatory environment. Collectively, these data reveal a novel SLC program activated during efferocytosis, identify a previously unknown reliance on aerobic glycolysis during apoptotic cell uptake, and that glycolytic byproducts of efferocytosis can also influence other cells in the microenvironment.
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| Overall design |
The experiment consisted of two conditions: Phagocytes (LR73 cells) alone or co-cultured with apoptotic Jurkat lymphoma cells. Each condition consisted of four biological replicates.
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| Contributor(s) |
Morioka S, Perry JS, Raymond MH, Medina CB, Zhu Y, Zhao L, Serbulea V, Onengut-Gumuscu S, Leitinger N, Kucenas S, Rathmell JC, Makowski L, Ravichandran KS |
| Citation(s) |
30464343 |
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| Submission date |
Aug 30, 2018 |
| Last update date |
Nov 30, 2018 |
| Contact name |
Justin Shaun Arnold Perry |
| E-mail(s) |
perryj@mskcc.org
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| Phone |
6468883928
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| Organization name |
Sloan Kettering Institute for Cancer Research
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| Department |
Immunology Program
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| Lab |
Perry Lab
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| Street address |
408 East 69th Street, 408-15
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| City |
New York |
| State/province |
New York |
| ZIP/Postal code |
10065 |
| Country |
USA |
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| Platforms (1) |
| GPL22327 |
Illumina NextSeq 500 (Cricetulus griseus) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA488640 |
| SRA |
SRP159189 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE119273_LR73_AC_results.txt.gz |
1.0 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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