A high proliferation rate is required for cell reprogramming and maintenance of human embryonic stem cell identity

Sergio Ruiz, Athanasia D. Panopoulos, Aída Herrerías, Karl Dimiter Bissig, Margaret Lutz, W. Travis Berggren, Inder M. Verma, Juan Carlos Izpisua Belmonte

Research output: Contribution to journalArticlepeer-review

203 Scopus citations

Abstract

Human embryonic stem (hES) cells show an atypical cell-cycle regulation characterized by a high proliferation rate and a short G1 phase [1,2]. In fact, a shortened G1 phase might protect ES cells from external signals inducing differentiation, as shown for certain stem cells [3]. It has been suggested that self-renewal and pluripotency are intimately linked to cell-cycle regulation in ES cells [4-6], although little is known about the overall importance of the cell-cycle machinery in maintaining ES cell identity. An appealing model to address whether the acquisition of stem cell properties is linked to cell-cycle regulation emerged with the ability to generate induced pluripotent stem (iPS) cells by expression of defined transcription factors [7-11]. Here, we show that the characteristic cell-cycle signature of hES cells is acquired as an early event in cell reprogramming. We demonstrate that induction of cell proliferation increases reprogramming efficiency, whereas cell-cycle arrest inhibits successful reprogramming. Furthermore, we show that cell-cycle arrest is sufficient to drive hES cells toward irreversible differentiation. Our results establish a link that intertwines the mechanisms of cell-cycle control with the mechanisms underlying the acquisition and maintenance of ES cell identity.

Original languageEnglish (US)
Pages (from-to)45-52
Number of pages8
JournalCurrent Biology
Volume21
Issue number1
DOIs
StatePublished - Jan 11 2011

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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