Literatür Detay Bilgisi
Downregulation of Dicer1 promotes cellular senescence and decreases the differentiation and stem cell-supporting capacities of mesenchymal stromal cells in patients with myelodysplastic syndrome.

Yazarlar : Zhao Y, Wu D, Fei C et al

Yayın : Haematologica.

Yayın Yılı : 2014

Pubmed Linki : http://www.ncbi.nlm.nih.gov/pubmed/25361944

Konu : MDS

Literatür İçeriği :  

Abstract

Although the insufficient hematopoietic support capabilities of mesenchymal stromal cells have been reported in myelodysplastic syndrome, the underlying mechanisms remain elusive. In this study, we found that mesenchymal stromal cells from patients with myelodysplastic syndromedisplayed a significant increase in senescence, as evidenced by their decreased proliferative capacity, flattened morphology and increased expression of SA-β-gal and p21. Senescent mesenchymal stromal cells from patients exhibited decreased differentiation potential and decreased stem cell support capacity. Gene knockdown of Dicer1,which was down-regulated in mesenchymal stromal cells from patients, induced senescence. The differentiation and stem cell-supporting capacities were significantly inhibited by Dicer1 knockdown. Overexpression of Dicer1 in mesenchymal stromal cells from patients reversed cellular senescence and enhanced stem cell properties. Further, we identified reduced expression in the miR-17 family (miR-17-5p, miR-20a/b, miR-106a/b and miR-93) as a potential factor responsible for increased p21 expression, a key senescence mediator, in Dicer1 knockdown cells. Moreover, we found that miR-93 and miR-20a expression levels were significantly reduced in mesenchymal stromal cells from patients and miR-93/miR-20a gain of function resulted in a decrease of cellular senescence. Taken together, our study shows that mesenchymal stromal cells from patients with myelodysplastic syndrome are prone to senescence and that Dicer1 downregulation promotes cellular senescence and decreases the differentiation and stem cell-supporting capacities of mesenchymal stromal cells. Dicer1 downregulation seems to contribute to the insufficient hematopoietic support capacities of mesenchymal stromal cells from patients withmyelodysplastic syndrome.

Copyright © 2014, Ferrata Storti Foundation.


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