title: Robust cellular reprogramming occurs spontaneously during liver regeneration.
abstract: Cellular reprogramming-the ability to interconvert distinct cell types with defined factors-is transforming the field of regenerative medicine. However, this phenomenon has rarely been observed in vivo without exogenous factors. Here, we report that activation of Notch, a signaling pathway that mediates lineage segregation during liver development, is sufficient to reprogram hepatocytes into biliary epithelial cells (BECs). Moreover, using lineage tracing, we show that hepatocytes undergo widespread hepatocyte-to-BEC reprogramming following injuries that provoke a biliary response, a process requiring Notch. These results provide direct evidence that mammalian regeneration prompts extensive and dramatic changes in cellular identity under injury conditions.
authors.affiliation: Department of Medicine, Gastroenterology Division.
authors.forename: Kilangsungla
authors.initials: K
authors.lastname: Yanger
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Zong
authors.forename: Lara R
authors.initials: LR
authors.lastname: Maggs
authors.forename: Suzanne N
authors.initials: SN
authors.lastname: Shapira
authors.forename: Ravi
authors.initials: R
authors.lastname: Maddipati
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Aiello
authors.forename: Swan N
authors.initials: SN
authors.lastname: Thung
authors.forename: Rebecca G
authors.initials: RG
authors.lastname: Wells
authors.forename: Linda E
authors.initials: LE
authors.lastname: Greenbaum
authors.forename: Ben Z
authors.initials: BZ
authors.lastname: Stanger
mesh_terms: D000818:Animals; D019070:Cell Lineage; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism; D008115:Liver Regeneration / Q000502:physiology*; D051379:Mice; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology
chemical_list: D051880:Receptors, Notch