생화학분자생물학회

	In-Hyun Park ( inhyun.park@yale.edu )
	2015-present	Associate Professor, Department of Genetics, Yale University
	2009-2015	Assistant Professor, Department of Genetics, Yale University
	2005-2009	Research Fellow, Biological Chemistry and Molecular Pharmacology, Harvard Medical School, USA
	2000-2005	Ph.D., Department of Cell and Structural Biology, Univ. of Illinois at Urbana, USA

Generation, Differentiation, and the Potential of Three Radial Glial Subtypes in Human Cortical Organoids

Radial glia are the principal neural stem cells in the developing human cerebral cortex and have been classified as three molecularly distinct subtypes: ventricular radial glia (vRG), outer radial glia (oRG), and truncated radial glia (tRG). Human cortical organoids (hCOs) from human pluripotent stem cells that recapitulate the developmental program of human cortex have shown this progenitor diversity. vRG and oRG are readily generated and identified in hCOs from most differentiation protocols with oRG emergence dependent on specific signaling pathway, such as LIF/STAT3 supplementation. However, tRGs that have only recently been defined at the molecular level have not been systematically examined in any organoid system. Here we review the biology, signaling, and lineage potential of each radial glial subtype and assess how faithfully they are represented in cortical organoids. We highlight and discuss the studies on the tRG from hCOs. We discuss data that support the presence of tRG in hCOs, including ependymal cell generation from radial glia within organoids, CRYAB-positive progenitors in three-dimensional culture systems, and tRG-associated transcriptomic change upon genetic perturbation. However, definitive identification through combinatorial marker co-expression and morphological validation has not yet been achieved. Faithfully establishing molecular signatures and signaling frameworks for tRG and their existence in hCOs will provide the foundation for systemically investigating the development and function of this cell type in vitro. We discuss future directions for resolving whether tRG is generated during the neurogenesis-to-gliogenesis transition.

BMB Rep. 2026 Jul 9:6811. Online ahead of print.
https://pubmed.ncbi.nlm.nih.gov/42420164/