Generating human neural diversity with a multiplexed morphogen screen in organoids.

ABSTRACT: Morphogens choreograph the generation of remarkable cellular diversity in the developing nervous system. Differentiation of stem cells in vitro often relies upon the combinatorial modulation of these signaling pathways. However, the lack of a systematic approach to understand morphogen-directed differentiation has precluded the generation of many neural cell populations, and the general principles of regional specification and maturation remain incomplete. Here, we developed an arrayed screen of 14 morphogen modulators in human neural organoids cultured for over 70 days. Deconvolution of single-cell-multiplexed RNA sequencing data revealed design principles of brain region specification. We tuned neural subtype diversity to generate a tachykinin 3 (TAC3)-expressing striatal interneuron typ

SUBMITTER: Amin ND 

PROVIDER: S-EPMC12302009 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature