Molecular and Cellular Mechanisms Linking Cell-to-Cell Variation to Pluripotency > 세미나

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Molecular and Cellular Mechanisms Linking Cell-to-Cell Variation to Pl…

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  • 최고관리자
  • 2017-10-16


[Life Sciences / IBB Faculty Candidate Seminar]

▶Subject: Molecular and Cellular Mechanisms Linking Cell-to-Cell Variation to Pluripotency

▶Speaker: Jiwon Jang, Ph.D. (University of California Santa Barbara)
▶Date: 4:00PM/Oct. 24(Tue.)/2017

▶Place: Auditorium(1F), Postech Biotech Center
Embryonic development is a process of creating heterogeneity. Hundreds of different cell fates are generated from a zygote during development. In model organisms, non-cell-autonomous mechanisms such as morphogen gradients have been extensively studied. However, our knowledge about cell-autonomous mechanisms contributing to heterogeneity is limited. In this talk, I suggest that human embryonic stem cell (hESC) populations utilize intrinsic variation in single cell G1 length to generate multiple fates upon differentiation. Single hESCs have different and biased differentiation potentials toward either neuroectoderm or mesendoderm depending on their G1 lengths even before the onset of differentiation. Therefore, single cell variation in G1 length establishes a probability distribution that determines the fate of the population. Environmental levels of WNT control the amount of G1 length variation and consequently influence differentiation outcomes of hESC populations. Furthermore, I suggest that a Primary cilium-Autopahgy-Nrf2 (PAN) axis is the earliest cascade of triggering events during hESC differentiation and links G1 length to differentiation fates of stem cells. Coupled with lineage-specific lengthening of G1 phase a divergent ciliation pattern emerged within the first 24 hours of induced lineage specification and these changes drive a neuroectoderm decision before any neural precursor markers were expressed. By day 2, increased ciliation in neuroectoderm precursors induced autophagy that resulted in the inactivation of Nrf2 (NFE2L2) and thereby relieved transcriptional activation of OCT4 and NANOG. Nrf2 binds directly to upstream regions of these pluripotency genes to promote their expression and repress neuroectoderm derivation. Only after these events had been initiated do neural precursor markers get expressed at day 4. Thus we have identified a Primary cilium-Autopahgy-Nrf2 (PAN) control axis working upstream of the pluripotency genes that link G1 length variation to early differentiation fates of hESCs. All together, these findings suggest single cell variation in G1 length and a PAN axis as novel mechanisms through which hESCs create heterogeneity during differentiation

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