Forward programming human pluripotent stem cells into microglia

Abstract

Microglia play vital roles in embryonic and post-natal development, homeostasis, and pathogen defence in the central nervous system. Human induced pluripotent stem cell (hiPSC)-based methods have emerged as an important source for the study of human microglia in vitro. Classical approaches to differentiate hiPSCs into microglia suffer from limitations including extended culture periods, consistency, and efficiency. More recently, forward programming has arisen as a promising alternative for the manufacture of bulk quantities of human microglia. This review provides a comprehensive assessment of published forward programming protocols that are based on forced expression of key lineage transcription factors (TFs). We focus on the choice of reprogramming factors, transgene delivery methods, and medium composition, which impact induction kinetics and the resulting microglia phenotype.

Keywords: cell engineering; differentiation; genome engineering; microglia; reprogramming; stem cells; transcription factors.