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sciadv.adg4055.pdf (2.29 MB)

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2023-07-14

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cc by (c) Hansen, Stine L. et al, 2023
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/205422

An organoid-based CRISPR-Cas9 screen for regulators of intestinal epithelial maturation and cell fate

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https://doi.org/10.1126/sciadv.adg4055

Resum

Generation of functionally mature organs requires exquisite control of transcriptional programs governing cell state transitions during development. Despite advances in understanding the behavior of adult intestinal stem cells and their progeny, the transcriptional regulators that control the emergence of the mature intestinal phenotype remain largely unknown. Using mouse fetal and adult small intestinal organoids, we uncover transcriptional differences between the fetal and adult state and identify rare adult-like cells present in fetal organoids. This suggests that fetal organoids have an inherent potential to mature, which is locked by a regulatory program. By implementing a CRISPR-Cas9 screen targeting transcriptional regulators expressed in fetal organoids, we establish Smarca4 and Smarcc1 as important factors safeguarding the immature progenitor state. Our approach demonstrates the utility of organoid models in the identification of factors regulating cell fate and state transitions during tissue maturation and reveals that SMARCA4 and SMARCC1 prevent precocious differentiation during intestinal development.

Matèries

Cèl·lules mare, Intestins

Matèries (anglès)

Stem cells, Intestines

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Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citació

HANSEN, Stine l., LARSEN, Hjalte l., PIKKUPEURA, Laura m., MACIAG, Grzegorz, GUIU, Jordi, MÜLLER, Iris, CLEMENT, Ditte l., MUELLER, Christina, JOHANSEN, Jens vilstrup, HELIN, Kristian, LERDRUP, Mads, JENSEN, Kim b.. An organoid-based CRISPR-Cas9 screen for regulators of intestinal epithelial maturation and cell fate. _Science Advances_. 2023. Vol. 9, núm. 28. [consulta: 29 de gener de 2026]. ISSN: 2375-2548. [Disponible a: https://hdl.handle.net/2445/205422]

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