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Morphological and molecular changes of human granulosa cells exposed to 5-azacytidine and addressed toward muscular differentiation.

Abstract：

:Converting adult cells from one cell type to another is a particularly interesting idea for regenerative medicine. Terminally differentiated cells can be induced to de-differentiate in vitro to become multipotent progenitors. In mammals these changes do not occur naturally, however exposing differentiated adult cells to synthetic molecules capable of selectively reverting cells from their lineage commitment to a more plastic state makes it possible to re-address their fate. Only scattered information are available on the morphological changes and ultrastructural remodeling taking place when cells convert into a different and specific type. To better clarify these aspects, we derived human granulosa cell (GC) primary cultures and analyzed the morphological changes taking place in response to the exposure to the epigenetic modifier 5-azacytidine (5-aza-CR) and to the treatment with VEGF, as a stimulus for inducing differentiation into muscle cells. Ultrastructural modifications and molecular marker expression were analyzed at different intervals during the treatments. Our results indicate that the temporary up regulation of pluripotency markers is accompanied by the loss of GC-specific ultrastructural features, mainly through autophagocitosis, and is associated with a temporary chromatin decondensation. After exposure to VEGF the induction of muscle specific genes was combined with the appearance of multinucleated cells with a considerable quantity of non-spatially organized filaments. The detailed analysis of the morphological changes occurring in cells undergoing lineage re-addressing allows a better understanding of these process and may prove useful for refining the use of somatic cells in regenerative medicine and tissue replacement therapies.

journal_name

Stem Cell Rev Rep

journal_title

Stem cell reviews and reports

authors

Brevini TA,Pennarossa G,Rahman MM,Paffoni A,Antonini S,Ragni G,deEguileor M,Tettamanti G,Gandolfi F

doi

10.1007/s12015-014-9521-4

subject

Has Abstract

pub_date

2014-10-01 00:00:00

pages

633-42

issue

eissn

2629-3269

issn

2629-3277

journal_volume

pub_type

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Morphological and molecular changes of human granulosa cells exposed to 5-azacytidine and addressed toward muscular differentiation.