Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Journal stats
  • Publication ethics
  • Publication alerts by email
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Physician-Scientist Development
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • In-Press Preview
    • Resource and Technical Advances
    • Clinical Research and Public Health
    • Research Letters
    • Editorials
    • Perspectives
    • Physician-Scientist Development
    • Reviews
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Resource and Technical Advances
  • Clinical Research and Public Health
  • Research Letters
  • Editorials
  • Perspectives
  • Physician-Scientist Development
  • Reviews
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Journal stats
  • Publication ethics
  • Publication alerts by email
  • Transfers
  • Advertising
  • Job board
  • Contact
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
View: Text | PDF
Research Article Neuroscience Therapeutics

Preimplantation factor modulates oligodendrocytes by H19-induced demethylation of NCOR2

  • Text
  • PDF
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

×

Figure 1

sPIF induces oligodendrocyte differentiation markers in an H19-dependent manner.

Options: View larger image (or click on image) Download as PowerPoint
sPIF induces oligodendrocyte differentiation markers in an H19-dependent...
Hybrid cell line (MO3.13) that expresses phenotypic characteristics of primary oligodendrocytes in an immature developmental stage and rat oligodendrocyte precursor cells were incubated with sPIF (100 and/or 200 nM or control — Ctrl). RNAs and proteins were extracted 48 hours later, and levels were determined by qRT-PCR (A and C) and Western blots (B and C: representative Western blots). (D and E) Cells were transfected with control siRNA (siCtrl) or siRNA specific for H19 (siH19) or incubated with sPIF at 100 and/or 200 nM or Ctrl. RNAs were harvested 48 hours after transfection and analyzed by qRT-PCR. (F) Cells were transfected with control siRNA (siCtrl) and/or control miRNA (siCon) and siRNA specific for H19 (siH19) or let-7 inhibitor (iLet7), and RNAs were harvested 48 hours after transfection and analyzed by qRT-PCR. Results are presented as mean ± SEM and are representative of at least 3 independent experiments. Single comparisons with Ctrl were made using a 2-tailed Student’s t test or Mann-Whitney test with Bonferroni’s correction. **P < 0.005; ***P < 0.0005. The levels of Ctrl and siCtrl were arbitrarily set to 1. Protein levels are presented after normalization to actin. Each experiment was conducted at least 3 times.

Copyright © 2026 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts