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Direct reprogramming of human umbilical vein- and peripheral blood-derived endothelial cells into hepatic progenitor cells
- Source :
- Nature Communications, Vol 11, Iss 1, Pp 1-17 (2020), Nature Communications
- Publication Year :
- 2020
- Publisher :
- Nature Portfolio, 2020.
-
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.<br />The conditions to induce human hepatic progenitor cells from other cell types are unclear. Here, the authors reprogram human endothelial cells to hepatic progenitor cells by expressing FOXA3, HNF1A and HNF6, capable of giving rise to hepatocytes and cholangiocytes that reconstitute damaged liver tissues on transplantation.
- Subjects :
- 0301 basic medicine
Male
Somatic cell
Cell
General Physics and Astronomy
Stem cells
Mice, SCID
Umbilical vein
Mice
0302 clinical medicine
Mice, Inbred NOD
Cellular Reprogramming Techniques
Hepatocyte Nuclear Factor 1-alpha
lcsh:Science
Cells, Cultured
Cell Aggregation
Multidisciplinary
Cell Differentiation
Cellular Reprogramming
Cell aggregation
Cell biology
Hepatocyte Nuclear Factor 6
medicine.anatomical_structure
030220 oncology & carcinogenesis
Differentiation
Regenerative medicine
Heterografts
Female
Reprogramming
Cell type
Science
Biology
General Biochemistry, Genetics and Molecular Biology
Article
03 medical and health sciences
Spheroids, Cellular
medicine
Human Umbilical Vein Endothelial Cells
Regeneration
Animals
Humans
Progenitor cell
Endothelial Cells
General Chemistry
Transplantation
Mice, Inbred C57BL
030104 developmental biology
Hepatocytes
lcsh:Q
Bile Ducts
Hepatocyte Nuclear Factor 3-gamma
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 11
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....f978c8e4da8911d1ed422c909b682d50