Endogenous reactive oxygen species (ROS) and their downstream products, e.g. lipid peroxidation by- products, are emerging as central secondary messengers in cell fate signaling and are also connected to a number of pathological events. We have reveal an in vivo role for the endogenous product of lipid metabolism 9-hydroxystearic acid (9-HSA), in regulating the balance between cell proliferation and differentiation of progenitors cells (RPCs) specifically in the retina during the zebrafish eye development. We found that 9-HSA is endogenously produced in the zebrafish during normal embryonic development. It and its exogenous administration results in retinal differentiation defects coinciding with maintenance of progenitor cells in the S-phase of the cell cycle and the up-regulation of cell cycle regulators such as c-myc and cyclinD1 in the central retina. The oxidative state analyses of RSC within the RSC niche revealed the localized presence of ROS within a particular differentiating region of committed progenitors. Our work provides in vivo evidence of a physiological role of (R)-9-HSA in the regulation of stem cell maintenance and differentiation balance via the direct regulation of HDAC1 activity. Together our findings show that the oxidative stress cellular state regulates RSC fate and differentiation during retina development.

ROLE OF LIPID PEROXIDATION PRODUCT IN ZEBRAFISH DEVELOPMENT

CALONGHI, NATALIA;PAROLIN, CAROLA ELEONORA;NASO, FEDERICA;SARTOR, GIORGIO;
2017

Abstract

Endogenous reactive oxygen species (ROS) and their downstream products, e.g. lipid peroxidation by- products, are emerging as central secondary messengers in cell fate signaling and are also connected to a number of pathological events. We have reveal an in vivo role for the endogenous product of lipid metabolism 9-hydroxystearic acid (9-HSA), in regulating the balance between cell proliferation and differentiation of progenitors cells (RPCs) specifically in the retina during the zebrafish eye development. We found that 9-HSA is endogenously produced in the zebrafish during normal embryonic development. It and its exogenous administration results in retinal differentiation defects coinciding with maintenance of progenitor cells in the S-phase of the cell cycle and the up-regulation of cell cycle regulators such as c-myc and cyclinD1 in the central retina. The oxidative state analyses of RSC within the RSC niche revealed the localized presence of ROS within a particular differentiating region of committed progenitors. Our work provides in vivo evidence of a physiological role of (R)-9-HSA in the regulation of stem cell maintenance and differentiation balance via the direct regulation of HDAC1 activity. Together our findings show that the oxidative stress cellular state regulates RSC fate and differentiation during retina development.
2017
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Calonghi, N.; Parolin, C.; Naso, F.; Sartor, G.; Del Bene, F.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/591282
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