Histone Modifications Pattern Associated With a State of Mesenchymal Stem Cell Cultures Derived From Amniotic Fluid of Normal and Fetus‐Affected Gestations

• Published in: Journal of cellular biochemistry 2017-11, Vol.118 (11), p.3744-3755
• Main Authors: Savickienė, Jūratė, Matuzevičius, Dalius, Baronaitė, Sandra, Treigytė, Gražina, Krasovskaja, Natalija, Zaikova, Ilona, Navakauskas, Dalius, Utkus, Algirdas, Navakauskienė, Rūta
• Format: Article
• Language: English
• Subjects: Abnormalities; AMNIOTIC FLUID; Amniotic Fluid - cytology; Amniotic Fluid - metabolism; CD105 antigen; CD44 antigen; CD90 antigen; Cell surface; Cells, Cultured; Chromatin; Deoxyribonucleic acid; DNA; DNA methylation; DNMT1 protein; Embryo cells; EPIGENETICS; Female; Fetus - cytology; Fetus - metabolism; Fetuses; Gene expression; Gestation; HISTONE MODIFICATIONS; Histones - metabolism; Humans; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - metabolism; Mesenchyme; Oct-4 protein; Pregnancy; Pregnancy Trimester, Second - metabolism; Protein Processing, Post-Translational - physiology; Regenerative medicine; Regulatory mechanisms (biology); STEM CELLS
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.26022

ABSTRACT Human amniotic fluid (AF)‐derived mesenchymal stem cells (MSCs) sharing embryonic and adult stem cells characteristics are interesting by their multipotency and the usage for regenerative medicine. However, the usefulness of these cells for revealing the fetal diseases still needs to be assessed. Here, we have analyzed the epigenetic environment in terms of histone modifications in cultures of MSCs derived from AF of normal pregnancies and those with fetal abnormalities. The comparison of MSCs samples from AF of normal pregnancies (N) and fetus‐affected (P) revealed two distinct cultures by their proliferation potential (P I and P II). Cell populations from N and P I samples had similar growth characteristics and exhibited quite similar cell surface (CD44, CD90, CD105) and stemness markers (Oct4, Nanog, Sox2, Rex1) profile that was distinct in slower growing and faster senescent P II cultures. Those differences were associated with changes in 5‐Cyt DNA methylation and alterations in the expression levels of chromatin modifiers (DNMT1, HDAC1/2), activating (H4ac, H3K4me3), and repressive (H3K9me2/me3, H3K27me3) histone marks. MSCs isolated from AF with the genetic or multifactorial fetal diseases (P II samples) were enriched with repressive histone marks and H4K16ac, H3K9ac, H3K14ac modifications. This study indicates that differential epigenetic environment reflects a state of AF‐MSCs dependently on their growth, phenotype, and stemness characteristics suggesting a way for better understanding of epigenetic regulatory mechanisms in AF‐MSCs cultures in normal and diseased gestation conditions. J. Cell. Biochem. 118: 3744–3755, 2017. © 2017 Wiley Periodicals, Inc. Our study indicates that differential epigenetic environment reflects a state of AF‐MSCs dependently on their growth, phenotype and stemness characteristics suggesting a way for better understanding of epigenetic regulatory mechanisms in AF‐MSCs cultures in normal and diseased gestation conditions.