TGFβ superfamily signaling regulates the state of human stem cell pluripotency and competency to create telencephalic organoids

摘要: SUMMARY Telencephalic organoids generated from human pluripotent stem cells (hPSCs) are emerging as an effective system to study the distinct features of developing brain and underlying causes many neurological disorders. While progress in organoid technology has been steadily advancing, challenges remain including rampant batch-to-batch cell line-to-cell line variability irreproducibility. Here, we demonstrate that a major contributor successful cortical production is manner which hPSCs maintained prior differentiation. Optimal results were achieved using fibroblast-feeder-supported compared feeder-independent cells, related differences their transcriptomic states. Feeder-supported display elevated activation diverse TGFβ superfamily signaling pathways increased expression genes associated with naive pluripotency. We further identify combinations TGFβ-related growth factors necessary together sufficient impart broad telencephalic competency feeder-free enable reproducible formation structures suitable for disease modeling. HIGHLIGHTS hPSC maintenance conditions influence outcomes Identification intermediate pluripotency state optimal Feeder support involves The organoid-promoting effects feeders can be mimicked by factor mixture