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Generation of the organotypic kidney structure by integrating pluripotent stem cell-derived renal stroma

Author

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  • Shunsuke Tanigawa

    (Kumamoto University)

  • Etsuko Tanaka

    (Kumamoto University)

  • Koichiro Miike

    (Kumamoto University)

  • Tomoko Ohmori

    (Kumamoto University)

  • Daisuke Inoue

    (Kumamoto University)

  • Chen-Leng Cai

    (Indiana University School of Medicine)

  • Atsuhiro Taguchi

    (Kumamoto University
    Max Planck Institute for Molecular Genetics)

  • Akio Kobayashi

    (Kumamoto University)

  • Ryuichi Nishinakamura

    (Kumamoto University)

Abstract

Organs consist of the parenchyma and stroma, the latter of which coordinates the generation of organotypic structures. Despite recent advances in organoid technology, induction of organ-specific stroma and recapitulation of complex organ configurations from pluripotent stem cells (PSCs) have remained challenging. By elucidating the in vivo molecular features of the renal stromal lineage at a single-cell resolution level, we herein establish an in vitro induction protocol for stromal progenitors (SPs) from mouse PSCs. When the induced SPs are assembled with two differentially induced parenchymal progenitors (nephron progenitors and ureteric buds), the completely PSC-derived organoids reproduce the complex kidney structure, with multiple types of stromal cells distributed along differentiating nephrons and branching ureteric buds. Thus, integration of PSC-derived lineage-specific stroma into parenchymal organoids will pave the way toward recapitulation of the organotypic architecture and functions.

Suggested Citation

  • Shunsuke Tanigawa & Etsuko Tanaka & Koichiro Miike & Tomoko Ohmori & Daisuke Inoue & Chen-Leng Cai & Atsuhiro Taguchi & Akio Kobayashi & Ryuichi Nishinakamura, 2022. "Generation of the organotypic kidney structure by integrating pluripotent stem cell-derived renal stroma," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28226-7
    DOI: 10.1038/s41467-022-28226-7
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    References listed on IDEAS

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    1. Matthew B. Buechler & Rachana N. Pradhan & Akshay T. Krishnamurty & Christian Cox & Aslihan Karabacak Calviello & Amber W. Wang & Yeqing Angela Yang & Lucinda Tam & Roger Caothien & Merone Roose-Girma, 2021. "Cross-tissue organization of the fibroblast lineage," Nature, Nature, vol. 593(7860), pages 575-579, May.
    2. Lu Han & Praneet Chaturvedi & Keishi Kishimoto & Hiroyuki Koike & Talia Nasr & Kentaro Iwasawa & Kirsten Giesbrecht & Phillip C. Witcher & Alexandra Eicher & Lauren Haines & Yarim Lee & John M. Shanno, 2020. "Single cell transcriptomics identifies a signaling network coordinating endoderm and mesoderm diversification during foregut organogenesis," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
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    1. Jessica M. Vanslambrouck & Sean B. Wilson & Ker Sin Tan & Ella Groenewegen & Rajeev Rudraraju & Jessica Neil & Kynan T. Lawlor & Sophia Mah & Michelle Scurr & Sara E. Howden & Kanta Subbarao & Melissa, 2022. "Enhanced metanephric specification to functional proximal tubule enables toxicity screening and infectious disease modelling in kidney organoids," Nature Communications, Nature, vol. 13(1), pages 1-23, December.

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