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Induction and Pattern Formation

開催日 2014/9/11
時間 11:00 - 12:00
会場 Poster / Exhibition(Event Hall B)

The bona fide pluripotency toward reproducible human neurogenesis

  • P1-067
  • 加藤 英政 / Hidemasa Kato:1 平木 啓子 / Keiko Hiraki-Kamon:2 
  • 1:埼玉医大・ゲノム医学研究センター / Research Center for Genomic Medicine,Saitama Med Univ, Hidaka, Japan 2:広大・原医研・分子疫学 / Dept Mol Etiol, RIRBM, Hiroshima Univ, Hiroshima, Japan 

Modeling neurological diseases using patient-derived iPS cells offer unprecedented opportunities to study molecular pathways directly relevant to the disease within the proper cellular context when the affected neural cell type is faithfully reproduced in vitro. This common strategy for studying neurological diseases today is hardly achieved due to the currently low differentiation efficiency inherent to the majority of human pluripotent stem cells. We have been able to rectify this differentiation deficit of human iPS cells using the activity of TET1, an epigenetic regulator we found to be degraded both in human ES as well as iPS cells. To our surprise, TET1-introduction did not render the iPS cells into a "naive" pluripotency as expected but corrected the propensity of the current human iPS cells to tilt toward mesendoderm lineage and placed these cells to the proper "primed" state. Most importantly, TET1-introduced human iPS cells exhibited reproducibly higher differentiation efficiency toward neural lineages. TET1 was also acting in silencing retrotransposon-related transcription, a feature recently found to be common to differentiation-deficient human iPS cells. We also found using mouse ES cells that Tet1 is operating by smoothening early exit from pluripotency. Together, we propose new criteria for human pluripotency and show examples of exploiting TET1 in manufacturing differentiation-proof human iPS cells. To understand this novel picture of human pluripotency, we will be discussing our findings in the light of some new ideas. The chronological value, which is a temporal value of the supposed master clock that all developing cells have to share among them, will be helpful in placing the bona fide human pluripotency in a temporal context during development. In addition, our new view of cell differentiation we coin here as "inheriting" differentiation will shed light to understand why the currently used criteria for demarcating pluripotency, such as expression of the so-called "pluripotency-related" markers is not sufficient to show true pluripotency. This will also help us to set a "standard" in manufacturing practicable human stem cells.

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