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Generation of trichogenic adipose-derived stem cells by expression of three factors

ABSTRACT: Generation of trichogenic adipose-derived stem cells by expression of three factors

PROVIDER: PRJNA480286 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7500740_1.fastq.gz	Fastqsanger.gz
	SRR7500740_2.fastq.gz	Fastqsanger.gz
	SRR7500741_1.fastq.gz	Fastqsanger.gz
	SRR7500741_2.fastq.gz	Fastqsanger.gz
	SRR7500742_1.fastq.gz	Fastqsanger.gz

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Generation of trichogenic adipose-derived stem cells by expression of three factors

Project description:Background: Previous studies demonstrated that adipose-derived stem cells (ASCs) can promote hair growth, but unmet needs exist for enhancing ASC hair inductivity. Objective: Therefore, we introduced three trichogenic factors platelet-derived growth factor-A, SOX2, and β-catenin to ASCs (tfASCs) and evaluated whether tfASCs have similar characteristics as dermal papilla (DP) cells. Method: Global gene expression was examined using NGS analysis. Telogen-to-anagen induction, vibrissae hair follicle organ culture and patch assay were used. Results: tfASC cell size is smaller than that of ASCs, and they exhibit short doubling time. tfASCs also resist aging and can be expanded until passage 12. Cell proportion in S and G2/M increases in tfASCs, and tfASCs express high mRNA levels of cell cycle related genes. The mRNA expression of DP markers was notably higher in tfASCs. Moreover, NGS analysis revealed that the global gene expression of tfASCs is similar to that of DP cells. The injection of tfASCs accelerated the telogen-to-anagen transition and conditioned medium of tfASCs increased the anagen phase of vibrissal hair follicles. Finally, we found that the injection of 3D-cultured tfASCs at p 9 generated new hair follicles in nude mice. Conclusion: Collectively, these results indicate that 1) tfASCs have similar characteristics as DP cells, 2) tfASCs have enhanced hair-regenerative potential compared with ASCs, and 3) tfASCs even at late passage can make new hair follicles in a hair reconstitution assay. Because DP cells are difficult to isolate/expand and ASCs have low hair inductivity, tfASCs and tfASC-CM are clinically good candidates for hair regeneration.

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Project description:Mesenchymal stem cells (MSCs) have therapeutic potential in various diseases, including myocardial infarction. Recently, the importance of the therapeutic effects of secreted factors from MSCs is increasing, but their identification has not progressed. In this study, we uncover the secreted protein profiles of MSCs derived from bone marrow, adipose tissue and dental pulp. Shotgun proteome analysis of conditioned MSC media by mass spectrometry identified 1533 proteins totally and 124 secreted proteins commonly produced among all three MSCs. The commonly secreted factors include already well-known factors whose functions are linked to MSCs’ biological effects, such as CTGF, SERPINE1, TGFB1, DKK3 and MYDGF, and also include newly identified factors whose roles are not well investigated, for example AIMP1, CLEC11A, GAS6, HDGF, INHBA, and PCSK5. Computational biological pathway analysis revealed that these common factors strongly relate to tissue regeneration pathways such as angiogenesis, migration, and inflammatory response. Further analysis showed enrichment of ossification, sprouting, and organ survival factors, suggesting connection to the functions closely related to MSCs’ therapeutic effects. This list of commonly secreted proteins could provide a reliable resource of biological factors which explain various effects of MSCs and would be useful for identifying new therapeutic factors produced from MSCs.

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