How equipotent cells develop into complex tissues containing many diverse cell types is one of the most fundamental as well as most important question in biology. The organisation of a cell’s interior, the cytoskeleton and organelles, is pivotal for every cell’s functionality. However, unlike most differentiated cells, our knowledge about the contribution of the sub-cellular architecture to pluripotency remains scarce.
Using cutting-edge live imaging, we discovered polarised non-centrosomal microtubules as central player for the pluripotent state of the in vivo early mammalian embryo and human induced pluripotent stem cells (hiPSCs). Contrary to the textbook view that microtubules radiate symmetrically from the centrosome to the periphery of a cell, the microtubules of the preimplantation embryo grow from the so called “interphase bridges” asymmetrically from one side of the cell to the other. These non-centrosomal microtubules, anchored and nucleated by the non-centrosomal microtubule minus end marker calmodulin-regulated spectrin-associated protein 3 (CAMSAP3), initiate an asymmetry of organelles and molecules, including RNAs, as cells become more specialised in vivo and in vitro. In addition, we have successfully engineered an optogenetical-controllable CAMSAP3-Halo (= Opto-CAMSAP3-Halo) cassette to translocate the origin of microtubule growth in pluripotent stem cells. Such light-inducible tools can overcome the current limitations of typical microtubule drugs to non-invasively and with spatial-temporal precision manipulate the organisation of the microtubule network and its direct link to the potency of stem cells in vivo and in vitro. Dissecting how intrinsic cellular regulation contributes to pluripotency will lead a revolutionary era of regenerative and reproductive medicine.