Systematic scRNA-seq screens profile neural organoid response to morphogens

  1. Fátima Sanchís-Calleja
  2. Nadezhda Azbukina
  3. Akanksha Jain
  4. Zhisong He
  5. Ryoko Okamoto
  6. Charlotte Rusimbi
  7. Pedro Rifes
  8. Gaurav Singh Rathore
  9. Malgorzata Santel
  10. Jasper Janssens
  11. Makiko Seimiya
  12. Benedikt Eisinger
  13. Jonas Simon Fleck
  14. Agnete Kirkeby
  15. J. Gray Camp
  16. Barbara Treutlein
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Abstract

Morphogens direct neuroepithelial fates toward discrete regional identities in vivo. Neural organoids provide models for studying neural regionalization through morphogen exposure; however, we lack a comprehensive survey of how the developing human neuroepithelium responds to morphogen cues. Here we produce a detailed survey of morphogen-induced effects on the regional specification of human neural organoids using multiplexed single-cell transcriptomic screens. We find that the timing, concentration and combination of morphogens strongly influence organoid cell-type and regional composition, and that cell line and neural induction method impact the response to a given morphogen condition. We apply concentration gradients in microfluidic chips or increasing static concentrations in multi-well plates and observe different patterning dynamics in each scenario. Altogether, we provide a detailed resource on neural lineage specification that, in combination with deep learning models, can enable the prediction of differentiation outcomes in human stem-cell-based systems.

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  1. Mentioned by @haoyin.bsky.social on Bluesky

    Neural organoid response (Cell type speciation, axial patterning) to morphogens A systematic scRNA-seq screening Round1️⃣ 👉8 morphogens (CHIR XAV939 SHH Cyclopamine FGF8b RA BMP4/7) 👉3 hPSC lines 👉97 conditions Round2️⃣ 👉Morphogen combos 👉12 conditions #NatMethods 2025 www.nature.com/articles/s41...

  2. Mentioned by @natmethods.nature.com on Bluesky

    A Resource paper provides a detailed atlas of morphogen-induced responses in human neural organoids. www.nature.com/articles/s41...

  3. Mentioned by @cedricboeckx.bsky.social on Bluesky

    New work from the Treutlein lab & @graycamplab.bsky.social, examining neural organoid response to morphogens 🧪🧠🧫🧬 www.nature.com/articles/s41...

  4. Mentioned by @neurowithmelike.bsky.social on Bluesky

    www.nature.com/articles/s41...

  5. Mentioned by @graycamplab.bsky.social on Bluesky

    Systematic scRNA-seq screens profile neural organoid response to morphogens. Collab. with Treutlein Lab! @natmethods.nature.com www.nature.com/articles/s41...

  6. Mentioned by @bigearthdata.ai on Bluesky

    Systematic scRNA-seq screens profile neural organoid response to morphogens ->Nature | More from Lil Dr Glen EcoChat at BigEarthData.ai

  7. Version published to 10.1038/s41592-025-02927-5
  8. Mentioned by @biorxiv-devbio.bsky.social on Bluesky

    Decoding morphogen patterning of human neural organoids with a multiplexed single-cell transcriptomic screen https://www.biorxiv.org/content/10.1101/2024.02.08.579413v1

  9. Mentioned by @biorxivpreprint.bsky.social on Bluesky

    Decoding morphogen patterning of human neural organoids with a multiplexed single-cell transcriptomic screen https://www.biorxiv.org/content/10.1101/2024.02.08.579413v1

  10. Version published to 10.1101/2024.02.08.579413v1 on bioRxiv