2016年度秋季学期学术系列讲座之十五
题目：Human iPS cells, pluripotency and developmental potential
讲座人：Rudolf Jaenisch, MD
Professor of Biology
Department of Biology, MIT
Whitehead Founding Member
Member of U.S. National Academy of Sciences
时间：2016年12月19日，13:00 - 14:30
地点：威廉希尔邓祐才报告厅
联系人：邓宏魁
摘要：
The development of the iPS cell technology has revolutionized our ability to study human diseases in defined in vitro cell culture systems. However, a number of issues need to be resolved and will be addressed in this talk.
1. State of pluripotency: Mouse ES and iPS cells appear to represent a naive state of pluripotency corresponding to the inner cell mass (ICM), whereas human ES or iPS cells represent the “primed” state corresponding to mouse EpiSCs. A major question is whether the naive state exists in the human system. We have, using an unbiased screening approach, generated ES cells that display a transcriptome similar to the human cleavage embryo. We have introduced the cells into mouse blastocysts in an effort to test for developmental potency. We were not successful to generate interspecies chimeras indicating that the cells can only inefficiently if at all functionally integrate into the developing mouse embryo.
2. Disease modeling and iPS cells: A major incentive of the iPS cell system is to model human diseases in the Petri dish. However, a serious concern is whether a 2D in vitro system can faithfully model complex human diseases. We are, therefore, using a 3D organoid system to study human brain development and CNS disorders. Ultimately, human diseases need to be studied under in vivo conditions. To this end we are establishing various approaches to generate mouse – human chimeras.
3. Neural Crest chimeras: To study the potential of committed stem to functionally integrate into the developing mouse embryos we have differentiated mouse, rat and human ESCs or iPSCs into NCCs that were injected in utero into E8.5 albino wild-type and c-Kit mutated Wsh/Wsh embryos. Both the mouse and human NCCs migrated laterally under the epidermis and ventrally into deeper regions of the embryo. Importantly, analysis of postnatal animals derived from mouse, rat or human NCC-injected embryos displayed coat color pigmentation from the donor cells. Our results demonstrate that NCCs from different species can integrate into the developing mouse embryo, migrate through the dermis and differentiate into functional pigment cells in postnatal mice. The generation of postnatal mouse/human chimeras carrying differentiated and functional human cells allows for a novel experimental system in which to study human diseases in an in vivo, developmentally-relevant environment.
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