Dataset Information

Proteomic analysis of small extracellular vesicles derived from human ESCs

ABSTRACT: Tissue-resident stem cell senescence leads to stem cell exhaustion, which is a major cause of physiological and pathological aging. Stem cells-derived extracellular vesicles(SCs-EVs) have been reported to possess therapeutic potential in preclinical studies for diverse diseases. However, whether SCs-EVs could rejuvenate senescent tissue stem cell to prevent age-related disorders still remains unknown. Here, we showed that chronic application of human embryonic stem cells-derived extracellular vesicles (hESCs-sEVs) rescues senescent bone marrow MSCs (BM-MSCs) function and prevents age-related bone loss in aging mice. Transcriptome analysis revealed that hESCs-sEVs treatment up-regulates the expression of genes involved in anti-aging, stem cell proliferation and osteogenic differentiation in BM-MSCs. Furthermore, liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis identified 4122 proteins encapsulated in hESCs-sEVs. Bioinformatics analysis predicated that protein components in the hESCs-sEVs function in a synergistic way to induce the activation of several canonical signaling pathways, including Wnt, Sirtuin, AMPK, PTEN signaling, which results in the up-regulation of anti-aging genes in BM-MSCs and then the recovery of senescent BM-MSCs function. Collectively, our findings reveal the effect of hESCs-sEVs in reversing BM-MSCs senescence and age-related osteogenic dysfunction, and thereby preventing age-related bone loss. Given that hESCs-sEVs could alleviate senescence of tissue-resident stem cells, it might be a promising therapeutic candidate for age-related diseases.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Embryonic Stem Cell

DISEASE(S): Osteoporosis

SUBMITTER: Liangzhi Gong

LAB HEAD: Yang Wang

PROVIDER: PXD018655 | Pride | 2021-08-30

REPOSITORIES: Pride

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Publications

Human ESC-sEVs alleviate age-related bone loss by rejuvenating senescent bone marrow-derived mesenchymal stem cells.

Gong Liangzhi L Chen Bi B Zhang Juntao J Sun Yongjin Y Yuan Ji J Niu Xin X Hu Guowen G Chen Yu Y Xie Zongping Z Deng Zhifeng Z Li Qing Q Wang Yang Y

Journal of extracellular vesicles 20200810 1

Tissue-resident stem cell senescence leads to stem cell exhaustion, which is a major cause of physiological and pathological ageing. Stem cell-derived extracellular vesicles (SC-EVs) have been reported in preclinical studies to possess therapeutic potential for diverse diseases. However, whether SC-EVs can rejuvenate senescent tissue stem cells to prevent age-related disorders still remains unknown. Here, we show that chronic application of human embryonic stem cell-derived small extracellular v ...[more]

PMID: 32944188

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Project description:Cyclic regeneration of the endometrium, and its repair after parturition or injury, are crucial for successful reproduction. Mesenchymal stem cells (MSCs) derived from bone marrow (BM-MSC) facilitate tissue repair via their secretome, which contains growth factors and cytokines that promote wound healing. Despite the implication of MSCs in endometrial regeneration and repair, the mechanisms remain unclear. This study tested the hypothesis that the secretome of MSCs from human BM upregulates human endometrial stromal cell (HESC) proliferation, migration and invasion, and activates pathways to increase HESC motility. MSCs were purchased from ATCC (BM-MSC-1) and cultured from the BM aspirate of a healthy female donor (BM-MSC-2). Indirect co-culture of MSCs and hTERT-immortalized HESCs via a transwell system studied the effect of the BM-MSC secretome on HESC proliferation, migration, and invasion. To study the effect of the MSC secretome on HESC gene expression, HESCs were exposed to the BM-MSC secretome via indirect co-culture for 24 h. Total RNA was extracted from HESCs for RNA sequencing (RNA-Seq). Differentially expressed genes (DEG) and significantly altered pathways were identified. Indirect co-culture of HESCs with BM- MSCs resulted in significant increase in HESC migration and invasion regardless of the source of MSCs. Effects on cellular proliferation varied among the BM-MSC source. Exposure of HESCs to the secretome of BM-MSCs changed the expression of 10,141 genes with FDR < 0.05. There was overlap among 4351 genes between HESCs exposed to BM-MSC-1 and BM-MSC-2, including upregulated expression of cell motility genes common to both BM-MSC exposures. Increased HESC motility by the secretome of BM-MSC appears to be mediated by paracrine and autocrine mechanisms, in part by modifying HESC gene expression. These data support the potential for leveraging the MSC secretome as a novel cell-free therapy in the treatment of disorders of endometrial regeneration.

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