AIBN Seminar Series: Understanding human reprogramming: a journey from epiblast and trophoblast into iBlastoids

We are pleased to present Professor Jose M Polo to speak on Understanding human reprogramming: a journey from epiblast and trophoblast into iBlastoids

Date: Thursday, 28th April

Time: 12:30pm - 1:30pm

Venue: AIBN Level 1 Seminar Room and Online Via Zoom

Click here to access the free seminar.

Abstract

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 (OSKM). These so called induced pluripotent stem cells (iPSCs), like embryonic stem cells (ESCs) 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, he molecular mechanisms of these transitions into primed or naive human-induced pluripotency remains poorly understood. To address this, we reconstructed the molecular reprogramming trajectories using single cell transcriptomics. This revealed that reprogramming into primed and naive human pluripotency follows diverging and distinct trajectories into the pluripotent states. 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 might transiently enter a TE-like state during reprogramming into naive pluripotency. We demonstrated that this transiently upregulated TE state can be stabilised by changing the culture condition, 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 allow to contact each other in a 3D culture, they self-organised giving rise to blastocyst-like structures which we have called iBlastoids. During my presentation, we will explore how these results provided a high-resolution roadmap for human reprogramming and novel insights into early human lineage specification, revealing an unanticipated role of the TE-lineage specific regulatory program during this process, facilitating the direct reprogramming of somatic cells into iTSCs and iBlastoids.

Presenter: Professor Jose M Polo

Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia

Jose Maria Polo was born in Buenos Aires, Argentina where he graduated from Buenos Aires University as a Biochemist. In 2002, Jose began his graduate studies at Albert Einstein College of Medicine, New York under the supervision of Dr. Ari Melnick where he worked on the transcriptional mechanism of the BCL6 repression complex in lymphomagenesis and B-cell maturation. In 2008, he obtained his PhD and moved to Boston to the laboratory of Dr. Konrad Hochedlinger at the Harvard Stem Cell Institute to work on reprogramming of adult cells into induced pluripotent stem (iPS) cells. In particular, his work focused on the acquisition of immortality and the existence of epigenetic memory during reprogramming.
In June 2011, established his independent research group at Monash University, where he holds appointments to the departments of Anatomy and Developmental Biology and to the Australian Regenerative Medicine Institute.  In 2012, Jose was awarded a NHMRC Career Development Fellowship, in 2014 a Silvia and Charles Viertel Senior Medical Research Fellowship and in 2018 an ARC Future Fellowship to continue his work in the molecular mechanism governing the reprogramming process and the epigenetic mechanism underpinning cell fate. In 2016, he co-founded Mogrify Ltd to translate reprogramming technologies into therapies, receiving several accolades including the 2019 Scrip Innovation Award.
In October 2021, Jose was recruited to the University of Adelaide as the inaugural Director of the Adelaide Centre for Epigenetics (ACE) and Program leader of the recently established South Australian Immunogenomics Cancer Institute (SAiGENCI). In Adelaide he will continue his work in epigenetics and its application to reprogramming, early embryogenesis and cancer.

Click here to join the Seminar Online