IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v11y2020i1d10.1038_s41467-020-19041-z.html
   My bibliography  Save this article

Direct reprogramming of human umbilical vein- and peripheral blood-derived endothelial cells into hepatic progenitor cells

Author

Listed:
  • Hiroki Inada

    (Kyushu University
    Kyushu University)

  • Miyako Udono

    (Kyushu University)

  • Kanae Matsuda-Ito

    (Kyushu University)

  • Kenichi Horisawa

    (Kyushu University)

  • Yasuyuki Ohkawa

    (Kyushu University)

  • Shizuka Miura

    (Kyushu University)

  • Takeshi Goya

    (Kyushu University
    Kyushu University)

  • Junpei Yamamoto

    (Kyushu University)

  • Masao Nagasaki

    (Kyoto University Graduate School of Medicine
    Kyoto University)

  • Kazuko Ueno

    (National Center for Global Health and Medicine)

  • Daisuke Saitou

    (Kyushu University)

  • Mikita Suyama

    (Kyushu University)

  • Yoshihiko Maehara

    (Kyushu University)

  • Wataru Kumamaru

    (Kyushu University)

  • Yoshihiro Ogawa

    (Kyushu University)

  • Sayaka Sekiya

    (Kyushu University)

  • Atsushi Suzuki

    (Kyushu University)

Abstract

Recent advances have enabled the direct induction of human tissue-specific stem and progenitor cells from differentiated somatic cells. However, it is not known whether human hepatic progenitor cells (hHepPCs) can be generated from other cell types by direct lineage reprogramming with defined transcription factors. Here, we show that a set of three transcription factors, FOXA3, HNF1A, and HNF6, can induce human umbilical vein endothelial cells to directly acquire the properties of hHepPCs. These induced hHepPCs (hiHepPCs) propagate in long-term monolayer culture and differentiate into functional hepatocytes and cholangiocytes by forming cell aggregates and cystic epithelial spheroids, respectively, under three-dimensional culture conditions. After transplantation, hiHepPC-derived hepatocytes and cholangiocytes reconstitute damaged liver tissues and support hepatic function. The defined transcription factors also induce hiHepPCs from endothelial cells circulating in adult human peripheral blood. These expandable and bipotential hiHepPCs may be useful in the study and treatment of human liver diseases.

Suggested Citation

  • Hiroki Inada & Miyako Udono & Kanae Matsuda-Ito & Kenichi Horisawa & Yasuyuki Ohkawa & Shizuka Miura & Takeshi Goya & Junpei Yamamoto & Masao Nagasaki & Kazuko Ueno & Daisuke Saitou & Mikita Suyama & , 2020. "Direct reprogramming of human umbilical vein- and peripheral blood-derived endothelial cells into hepatic progenitor cells," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19041-z
    DOI: 10.1038/s41467-020-19041-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-020-19041-z
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-020-19041-z?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Shizuka Miura & Kenichi Horisawa & Tokuko Iwamori & Satoshi Tsujino & Kazuya Inoue & Satsuki Karasawa & Junpei Yamamoto & Yasuyuki Ohkawa & Sayaka Sekiya & Atsushi Suzuki, 2024. "Hepatocytes differentiate into intestinal epithelial cells through a hybrid epithelial/mesenchymal cell state in culture," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19041-z. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.