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

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, Yoshihiko Maehara, Wataru Kumamaru, Yoshihiro Ogawa, Sayaka Sekiya and Atsushi Suzuki ()
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Hiroki Inada: 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
Junpei Yamamoto: Kyushu University
Masao Nagasaki: Kyoto University Graduate School of Medicine
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

Nature Communications, 2020, vol. 11, issue 1, 1-17

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-19041-z

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