Abnormalities in human pluripotent cells due to reprogramming mechanisms

Hong Ma, Robert Morey, Ryan C. O'Neil, Yupeng He, Brittany Daughtry, Matthew D. Schultz, Manoj Hariharan, Joseph R. Nery, Rosa Castanon, Karen Sabatini, Rathi D. Thiagarajan, Masahito Tachibana, Eunju Kang, Rebecca Tippner-Hedges, Riffat Ahmed, Nuria Marti Gutierrez, Crystal Van Dyken, Alim Polat, Atsushi Sugawara, Michelle SparmanSumita Gokhale, Paula Amato, Don P. Wolf, Joseph R. Ecker, Louise C. Laurent, Shoukhrat Mitalipov

Research output: Contribution to journalArticlepeer-review

207 Scopus citations

Abstract

Human pluripotent stem cells hold potential for regenerative medicine, but available cell types have significant limitations. Although embryonic stemcells (ES cells) frominvitro fertilizedembryos (IVFES cells) represent the 'gold standard', theyare allogeneic to patients. Autologous induced pluripotent stem cells (iPS cells) are prone to epigenetic and transcriptional aberrations. To determine whether such abnormalities are intrinsic to somatic cell reprogramming or secondary to the reprogramming method, genetically matched sets of human IVF ES cells, iPS cells and nuclear transfer ES cells (NT ES cells) derived by somatic cell nuclear transfer (SCNT) were subjected to genome-wide analyses. Both NT ES cells and iPS cells derived from the same somatic cells contained comparable numbers of de novo copy number variations. In contrast, DNA methylation and transcriptome profiles of NT ES cells corresponded closely to those of IVF ES cells, whereas iPS cells differed and retained residual DNA methylation patterns typical of parental somatic cells. Thus, human somatic cells can be faithfully reprogrammed to pluripotency by SCNTand are therefore ideal for cell replacement therapies.

Original languageEnglish (US)
Pages (from-to)177-183
Number of pages7
JournalNature
Volume511
Issue number7508
DOIs
StatePublished - 2014

ASJC Scopus subject areas

  • General

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