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ORGANOIDS

Not all cortical organoids are created equal

Nature Cell Biology volume 24, pages 805–806 (2022)Cite this article

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Multiple methods for deriving human cortical organoids have been established in the past decade. A study now systematically compares patterning strategies and shows that combined WNT and dual SMAD inhibition is superior to dual SMAD inhibition alone in inducing robust cortical identity in 3D human pluripotent stem-cell aggregates.

In the developing neural tube, regional identity emerges as a result of the intricate interplay among multiple components, including morphogens and cell–cell interactions. To mimic the spatio-temporal complexity of in vivo developmental dynamics, a combination of different inhibitors of key signalling pathways have been used to direct the differentiation of human pluripotent stem cells (hPSCs) into cortical organoids1. However, the contribution of individual signalling molecules has not yet been clarified, primarily due to the inaccurate perception that the patterning strategies used in different protocols generate the same compendium of cortical cell types. In the last few years, studies2 have begun to benchmark cortical organoids against single-cell datasets of the developing human cortex, however more comprehensive and rigorous comparisons across protocols used to derive human cortical organoids are required. In this issue of Nature Cell Biology, Rosebrock, Arora et al.3 uncover the essential role of WNT inhibition (WNT-i) paired with inhibition of TGFβ and BMP (dual SMAD-i) in instructing hPSC aggregates to adopt a cortical fate.

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Fig. 1: Dissecting in vivo developmental cues to improve modelling of human development and disease.

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Authors and Affiliations

  1. Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Alexander Atamian, Marcella Birtele & Giorgia Quadrato

  2. Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at the University of Southern California, Los Angeles, CA, USA

    Alexander Atamian, Marcella Birtele & Giorgia Quadrato

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  1. Alexander Atamian
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  2. Marcella Birtele
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  3. Giorgia Quadrato
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Correspondence to Giorgia Quadrato.

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The authors declare no competing interests.

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Atamian, A., Birtele, M. & Quadrato, G. Not all cortical organoids are created equal. Nat Cell Biol 24, 805–806 (2022). https://doi.org/10.1038/s41556-022-00890-3

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