Human amniotic epithelial cells are reprogrammed more efficiently by induced pluripotency than adult fibroblasts.
Cellular reprogramming from adult somatic cells into an embryonic cell-like state, termed induced pluripotency, has been achieved in several cell types. However, the ability to reprogram human amniotic epithelial cells (hAECs), an abundant cell source derived from discarded placental tissue, has only recently been investigated. Here we show that not only are hAECs easily reprogrammed into induced pluripotent stem cells (AE-iPSCs), but hAECs reprogram faster and more efficiently than adult and neonatal somatic dermal fibroblasts. Furthermore, AE-iPSCs express higher levels of NANOG and OCT4 compared to human foreskin fibroblast iPSCs (HFF1-iPSCs) and express decreased levels of genes associated with differentiation, including NEUROD1 and SOX17, markers of neuronal differentiation. To elucidate the mechanism behind the higher reprogramming efficiency of hAECs, we analyzed global DNA methylation, global histone acetylation, and the mitochondrial DNA A3243G point mutation. Whereas hAECs show no differences in global histone acetylation or mitochondrial point mutation accumulation compared to adult and neonatal dermal fibroblasts, hAECs demonstrate a decreased global DNA methylation compared to dermal fibroblasts. Likewise, quantitative gene expression analyses show that hAECs endogenously express OCT4, SOX2, KLF4, and c-MYC, all four factors used in cellular reprogramming. Thus, hAECs represent an ideal cell type for testing novel approaches for generating clinically viable iPSCs and offer significant advantages over postnatal cells that more likely may be contaminated by environmental exposures and infectious agents.
Division of Developmental and Regenerative Medicine, Departments of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh , Pittsburgh, PA 15213, USA.
Charles A
CA
Easley
Toshio
T
Miki
Carlos A
CA
Castro
John A
JA
Ozolek
Crescenzio F
CF
Minervini
Ahmi
A
Ben-Yehudah
Gerald P
GP
Schatten
D000328:Adult; D000650:Amnion / Q000166:cytology*; D000818:Animals; D002478:Cells, Cultured; D065150:Cellular Reprogramming / Q000502:physiology*; D004526:Efficiency; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000502:physiology*; D007231:Infant, Newborn; D000090062:Kruppel-Like Factor 4; D008297:Male; D051379:Mice; D016513:Mice, SCID; D011247:Pregnancy; D061251:Primary Cell Culture