Human neural progenitors establish a diffusion barrier in the ER membrane during cell division

Asymmetric segregation of cellular components regulates the fate and behavior of somatic stem cells. Similar to dividing budding yeast and precursor cells in C. elegans , it has been shown that mouse neural progenitors establish a diffusion barrier in the membrane of the endoplasmic reticulum (ER), which has been associated with asymmetric partitioning of damaged proteins and cellular age. However, the existence of an ER-diffusion barrier in human cells remains unknown. Here we used fluorescence loss in photobleaching (FLIP) imaging to show that human embryonic stem cell (hESC)- and induced pluripotent stem cell (iPSC)-derived neural progenitor cells establish an ER-diffusion barrier during cell division. The human ER-diffusion barrier is regulated via Lamin-dependent mechanisms and is associated with asymmetric segregation of mono- and polyubiquitinated, damaged proteins. Further, forebrain regionalized organoids derived from hESCs were used to show the establishment of an ER-membrane diffusion barrier in more naturalistic tissues mimicking early steps of human brain development. Thus, the data provided here show that human neural progenitors establish a diffusion barrier during cell division in the membrane of the ER, which may allow for asymmetric segregation of cellular components, contributing to the fate and behavior of human neural progenitor cells. Summary Human neural progenitors (NPCs) establish a diffusion barrier during cell division in the membrane of the endoplasmic reticulum, allowing for asymmetric segregation of cellular components, which may contribute to the fate and behavior of human NPCs.