Speaker: Professor Jose Polo

Title: Exploring the boundaries of human reprogramming

In 2007 Shinya Yamanaka demonstrated that human fibroblasts can be reverted back to a pluripotent state by the forced expression of four transcription factors; OCT4, SOX2, KLF4 and cMYC. These so called induced pluripotent stem cells (iPSCs), like embryonic stem cells derived from the epiblast of blastocysts, can give rise to any cell types of the body. Furthermore, iPSCs carry the promise of personalized regenerative medicine and hold tremendous potential for applications such as cell replacements therapeutics, disease modelling and in vitro drug screening. However, the molecular mechanisms of these cellular transitions into primed or naive human-induced pluripotency remained poorly understood. To address this, we reconstructed the molecular reprogramming trajectories using single cell transcriptomics. The integration of regulatory element usage with transcriptomics unveiled an unexpected role of trophectoderm (TE) lineage-associated transcription factors as well as a subpopulation of cells that transiently upregulated a TE-like signature during reprogramming. We demonstrated that this TE state could be stabilised allowing the derivation of induced Trophoblast Stem Cells (iTSCs). Further inspection of this cell cultures revealed also the upregulation of a primitive endoderm like signature in some of the cells. Unexpectedly, when all these cells are allowed to contact each other in a 3D culture, they self-organised giving rise to blastocyst-like structures which we have called iBlastoids. iBlastoids are capable of modelling in vitro, many molecular, morphological and functional aspects of embryonic development during the early stage of implantation. During my presentation, we will explore these findings as well as how reprogramming methods can be used beyond modelling early developmental pathways.

 

 

About Neuroscience Seminars

Neuroscience seminars at the QBI play a major role in the advancement of neuroscience in the Asia-Pacific region. The primary goal of these seminars is to promote excellence in neuroscience through the exchange of ideas, establishing new collaborations and augmenting partnerships already in place.

Seminars in the QBI Auditorium are held on Wednesdays at 12-1pm, which are sometimes simulcast on Zoom (with approval from the speaker). We also occassionally hold seminars from international speakers via Zoom. The days and times of these seminars will vary depending on the time zone of the speaker. Please see each seminar listed below for details. 

 

Neuroscience Seminars archive 2005-2018