Expanded stem cells enable large genetic screen of brain immune cell development

Researchers reporting in Nature established a platform that enabled screening of around 20,000 individual genetic perturbations to study how blood stem and progenitor cells develop into myeloid cells. Scarcity of primary cells had previously made large-scale genetic investigation impractical. The researchers expanded cells outside the body, genetically manipulated them and demonstrated that they could repopulate brain microglial niches after transplantation. Neonatal astrocytes also induced myeloid differentiation in culture. The screen identified Elp1 as essential for generating myeloid cells, but not maintaining them. The work establishes a research platform using mouse cells, with Elp1 suppressing the unfolded protein response during differentiation.