Optimal suppression of protein phosphatase 2A activity is critical for maintenance of human embryonic stem cell self-renewal

Byung Sun Yoon, Eun Kyoung Jun, Gyuman Park, Seung Jun Yoo, Jai Hee Moon, Cheong Soon Baik, Aeree Kim, Hyunggee Kim, Jong-Hoon Kim, Gou Young Koh, Hoon Taek Lee, Seungkwon You

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

The self-renewal of embryonic stem cells involves a balance between processes governed by crosstalk between intrinsic and extrinsic factors. We hypothesized that protein serine/threonine phosphatase 2A (PP2A) may play a central role in the signaling pathways that regulate human embryonic stem cell (hESC) self-renewal. Biochemical analyses revealed that PP2A activity gradually increases over the course of hESC differentiation; PP2A/C and PP2A/A levels also increased. The overexpression of PP2A/C or the addition of PP2A activator C2-ceramide promoted hESC differentiation. Accordingly, the addition of PP2A inactivator okadaic acid (OA) maintained hESC self-renewal in the absence of basic fibroblast growth factor (bFGF). The hESCs maintained with OA expressed pluripotency markers and exhibited substantial telomerase activity with normal karyotypes. The hESCs were able to differentiate into derivatives of the three germ layers, both in vitro and in vivo. Furthermore, the addition of OA and bFGF enabled the maintenance of hESC self-renewal without feeder cells, even in chemically defined xeno-free media. These findings shed a light on the role of PP2A in hESC differentiation and provide a novel strategy for maintaining the self-renewal capability of hESC in bFGF-free, feeder cell-free, and xeno-free media through the optimal suppression of PP2A activity using OA.

Original languageEnglish
Pages (from-to)874-884
Number of pages11
JournalStem Cells
Volume28
Issue number5
DOIs
Publication statusPublished - 2010 May 1

Keywords

  • Human embryonic stem cells
  • Okadaic acid
  • Protein phosphatase 2A
  • Self-renewal
  • Xeno-free

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Medicine

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