Preimplantation factor modulates oligodendrocytes by H19-induced demethylation of NCOR2
Marialuigia Spinelli, Celiné Boucard, Sara Ornaghi, Andreina Schoeberlein, Keller Irene, Daniel Coman, Fahmeed Hyder, Longbo Zhang, Valérie Haesler, Angelique Bordey, Eytan Barnea, Michael Paidas, Daniel Surbek, Martin Mueller
Marialuigia Spinelli, Celiné Boucard, Sara Ornaghi, Andreina Schoeberlein, Keller Irene, Daniel Coman, Fahmeed Hyder, Longbo Zhang, Valérie Haesler, Angelique Bordey, Eytan Barnea, Michael Paidas, Daniel Surbek, Martin Mueller
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Research Article Neuroscience Therapeutics

Preimplantation factor modulates oligodendrocytes by H19-induced demethylation of NCOR2

Abstract

Failed or altered gliogenesis is a major characteristic of diffuse white matter injury in survivors of premature birth. The developmentally regulated long noncoding RNA (lncRNA) H19 inhibits S-adenosylhomocysteine hydrolase (SAHH) and contributes to methylation of diverse cellular components, such as DNA, RNA, proteins, lipids, and neurotransmitters. We showed that the pregnancy-derived synthetic PreImplantation Factor (sPIF) induces expression of the nuclear receptor corepressor 2 (NCOR2) via H19/SAHH-mediated DNA demethylation. In turn, NCOR2 affects oligodendrocyte differentiation markers. Accordingly, after hypoxic-ischemic brain injury in rodents, myelin protection and oligodendrocytes’ fate are in part modulated by sPIF and H19. Our results revealed an unexpected mechanism of the H19/SAHH axis underlying myelin preservation during brain recovery and its use in treating neurodegenerative diseases can be envisioned.

Authors

Marialuigia Spinelli, Celiné Boucard, Sara Ornaghi, Andreina Schoeberlein, Keller Irene, Daniel Coman, Fahmeed Hyder, Longbo Zhang, Valérie Haesler, Angelique Bordey, Eytan Barnea, Michael Paidas, Daniel Surbek, Martin Mueller

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Figure 3

sPIF/H19 impacts oligodendrocyte differentiation in vivo.

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sPIF/H19 impacts oligodendrocyte differentiation in vivo. (A) Experiment...
(A) Experimental protocol indicating time points of electroporation, injury, treatment groups, and analyses. (B) Representative immunostainings of lateral ventricle (LV), cingulum, and partially caudate putamen at P3. The SVZ-labeled cells are red and SVZ/MASH1+ cells (differentiation marker) are indicated by yellow arrowheads (n = 3 each group). (C) Representative immunostainings of corpus callosum and deep cortical layers on P7. The SVZ/CNPase+ (left panels) or SVZ/OLIG2+ cells (right panels) representing oligodendrocyte precursors derived from SVZ-labeled cells are indicated by yellow arrowheads, and red arrowheads indicate examples of CNPase+ or OLIG2+ cells (n = 5 each group). (D) Quantification of immunostaining on P3 and P7 using percentage of SVZ-labeled cells coexpressing specific marker (n = 8 each group). SVZ, subventricular zone. Scale bars: 50 μm. All results are presented as mean ± SEM. **P < 0.01; ***P < 0.001 by 1-way repeated-measures ANOVA followed by Bonferroni’s multiple-comparison test.