Genome-wide expression microarray data of MCSP- and ABCB5-enriched CTCs
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ABSTRACT:
PROVIDER: PRJNA450337 | ENA |
REPOSITORIES: ENA
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Project description:Circulating Tumor Cells (CTCs) are shed from primary tumors into the bloodstream, mediating the hematogenous spread of cancer to distant organs. To determine the relevance of ECM protein expression to human disease, CTCs were isolated from the blood of metastatic PDAC patients and subjected to single cell RNA-sequencing. Analysis of 7 pancreatic CTCs from 3 patients revealed that the majority expressed keratins defining their epithelial origin. A total of 13 of 60 extracellular protein genes enriched in mouse CTCs (see GEO GSE51372) were expressed at high levels (>100 rpm) in at least one human pancreatic CTC. Human SPARC was the only gene found at high levels in all human pancreatic CTCs. To achieve a deep RNA sequencing profile of CTCs at the single cell level, we applied a novel inertial focusing-enhanced device, the CTC-iChip, which allows high efficiency negative depletion of normal blood cells, leaving unattached CTCs in solution where they can be selected and analyzed as single cells (Pubmed ID 23552373). CTCs were then subjected to single cell RNA-sequencing (Pubmed ID 20203668).
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Project description:Circulating Tumor Cells (CTCs) are shed from primary tumors into the bloodstream, mediating the hematogenous spread of cancer to distant organs. To determine the relevance of ECM protein expression to human disease, CTCs were isolated from the blood of metastatic PDAC patients and subjected to single cell RNA-sequencing. Analysis of 7 pancreatic CTCs from 3 patients revealed that the majority expressed keratins defining their epithelial origin. A total of 13 of 60 extracellular protein genes enriched in mouse CTCs (see GEO GSE51372) were expressed at high levels (>100 rpm) in at least one human pancreatic CTC. Human SPARC was the only gene found at high levels in all human pancreatic CTCs.
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Project description:Here we report the beneficial effects of a newly identified dermal cell subpopulation expressing the ATP-binding cassette subfamily B member 5 (ABCB5) for the therapy of non-healing wounds. Local administration of dermal ABCB5+-derived MSCs attenuated macrophage-dominated inflammation and thereby accelerated healing of full-thickness excisional wounds in the iron overload mouse model mimicking the non-healing state of human venous leg ulcers. The observed beneficial effects were due to interleukin-1 receptor antagonist (IL-1RA) secreted by ABCB5+-derived MSCs, which dampened inflammation and shifted the prevalence of unrestrained pro-inflammatory M1 macrophages towards repair promoting anti-inflammatory M2 macrophages at the wound site. The beneficial anti-inflammatory effect of IL-1RA released from ABCB5+-derived MSCs on human wound macrophages was conserved in humanized NOD-scid IL2rγnull mice. In conclusion, human dermal ABCB5+ cells represent a novel, easy accessible and marker-enriched source of MSCs which holds substantial promise to successfully treat chronic non-healing wounds in humans.
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