Schematic representation of two protocols used for the in vitro generation of PGC-like cells in mice and humans. Mouse embryonic stem cells (mESCs) are first converted to Epiblast-like cells (mEpiSCs) via activin and bFGF treatment, then mEpiSCs are differentiated to PGC-like cells using a combination of small molecules (BMP4, BMP8b, LIF, SCF, EGF). Human ESCs (hESCs) are converted to naïve hESCs using 4i medium and then differentiated to PGC-like cells using BMP2 or BMP4 in addition to LIF, SCF, EGF, and ROCK inhibitor. mPGC-like cells express high levels of T (Brachyury) and no Sox17, while hPGC-like cells express Sox17 and low levels of T (Brachyury).