A Chemically Defined Feeder-free System for the Establishment and Maintenance of the Human Naive Pluripotent State

Abstract

The distinct states of pluripotency in the pre- and post-implantation embryo can be captured in vitro as naive and primed pluripotent stem cell cultures, respectively. The study and application of the naive state remains hampered, particularly in humans, partially due to current culture protocols relying on extraneous undefined factors such as feeders. Here we performed a small-molecule screen to identify compounds that facilitate chemically defined establishment and maintenance of human feeder-independent naive embryonic (FINE) stem cells. The expression profile in genic and repetitive elements of FINE cells resembles the 8-cell-to-morula stage in vivo, and only differs from feeder-dependent naive cells in genes involved in cell-cell/cell-matrix interactions. FINE cells offer several technical advantages, such as increased amenability to transfection and a longer period of genomic stability, compared with feeder-dependent cells. Thus, FINE cells will serve as an accessible and useful system for scientific and translational applications of naïve pluripotent stem cells. © 2019 The Author(s)In this article, Chan and colleagues develop a chemically defined culture system for the establishment and maintenance of human feeder-independent naive embryonic (FINE) stem cells. FINE cells offer several technical advantages beyond feeder independence such as enhanced genomic stability, increased amenability to transfection, and expression of 8-cell-to-morula stage markers. © 2019 The Author(s)