CMM Seminar: Thursday, January 26, 2017

Day: Thursday,

Date: January 26, 2017

Time: 11:00-11:50 am

Location: CCRC Auditorium


Pluripotent stem cells (PSCs) are widely used to investigate human development and disease mechanisms. However,
under conventional culture conditions human PSCs do not resemble “naive” pluripotent cells found in the blastocyst, but
instead are regarded as more mature “primed” cells that are poised to differentiate. This has prompted interest in
capturing human PSCs that more closely resemble the naive ground state of the blastocyst. By screening a small molecule
library, I identified a combination of five kinase inhibitors that could induce defining features of naive pluripotency in
conventional human PSCs. To assess the correspondence between different stem cell states in vitro and human pluripotent
cells in vivo, I examined three molecular criteria: the collective expression of transposable elements, the genome-wide
DNA methylation landscape, and X chromosome status in female cells. This analysis revealed that naive human PSCs
adopt key molecular signatures of the pre-implantation embryo. The isolation of naive human PSCs presents a novel
model system to study mechanisms of early human development and X-linked diseases, and may enable the generation
of interspecies chimeras upon injection into the blastocyst of an animal host. I will discuss strategies to improve the longterm
stability of naive human PSCs and their potential applications in biomedical research.

Flyer for Seminar