Direct Lineage Reprogramming: Harnessing Cell Plasticity between Liver and Pancreas

Ruzittu, Silvia; Willnow, David; Spagnoli, Francesca M.

doi:10.1101/cshperspect.a035626

Cited by 9 publications

(17 citation statements)

References 118 publications

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“…5). Thus, our findings indicate sustained cell fate plasticity between progenitor populations as an important feature underlying hepato-pancreato-biliary development, instead of occurring as sequential binary cell fate decisions, as previously suggested 6, 8, 18 .…”

Section: Discussionsupporting

confidence: 82%

“…Similarly, deletion of Sox17 results in the appearance of Pdx1 + cells in the liver bud 20 , while genetic deficiency for Hes1 induces pancreatic fate in biliary tissues 37, 38 . In addition, fate switches have been reported in adult tissues upon injury, metabolic stress or in the context of rare cancer types 6, 8 , possibly recapitulating the developmental cell fate plasticity between hepatic and pancreato-biliary progenitors presented here.…”

Section: Discussionmentioning

confidence: 54%

“… SummarySingle cell-based studies have revealed tremendous cellular heterogeneity in stem cell and progenitor compartments, suggesting continuous differentiation trajectories with intermixing of cells at various states of lineage commitment and notable degree of plasticity during organogenesis 1–5 . The hepato-pancreato-biliary organ system relies on a small endoderm progenitor compartment that gives rise to a variety of different adult tissues, including liver, pancreas, gallbladder, and extra-hepatic bile ducts 6, 7 . Experimental manipulation of various developmental signals in the mouse embryo underscored an important cellular plasticity in this embryonic territory 6, 8 . This is also reflected in the existence of human genetic syndromes as well as congenital or environmentally-caused human malformations featuring multiorgan phenotypes in liver, pancreas and gallbladder 6, 8 .…”

mentioning

confidence: 99%

“…Experimental manipulation of various developmental signals in the mouse embryo underscored an important cellular plasticity in this embryonic territory 6, 8 . This is also reflected in the existence of human genetic syndromes as well as congenital or environmentally-caused human malformations featuring multiorgan phenotypes in liver, pancreas and gallbladder 6, 8 . Nevertheless, the precise lineage hierarchy and succession of events leading to the segregation of an endoderm progenitor compartment into hepatic, biliary, and pancreatic structures are not yet established.…”

mentioning

confidence: 99%

“…The hepato-pancreato-biliary organ system relies on a small endoderm progenitor compartment that gives rise to a variety of different adult tissues, including liver, pancreas, gallbladder, and extra-hepatic bile ducts 6, 7 . Experimental manipulation of various developmental signals in the mouse embryo underscored an important cellular plasticity in this embryonic territory 6, 8 . This is also reflected in the existence of human genetic syndromes as well as congenital or environmentally-caused human malformations featuring multiorgan phenotypes in liver, pancreas and gallbladder 6, 8 .…”

mentioning

confidence: 99%

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Quantitative lineage analysis identifies a long-term progenitor niche for the hepato-pancreato-biliary organ system

Willnow

Benary

Margineanu

et al. 2020

Preprint

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SummarySingle cell-based studies have revealed tremendous cellular heterogeneity in stem cell and progenitor compartments, suggesting continuous differentiation trajectories with intermixing of cells at various states of lineage commitment and notable degree of plasticity during organogenesis1–5.The hepato-pancreato-biliary organ system relies on a small endoderm progenitor compartment that gives rise to a variety of different adult tissues, including liver, pancreas, gallbladder, and extra-hepatic bile ducts6, 7. Experimental manipulation of various developmental signals in the mouse embryo underscored an important cellular plasticity in this embryonic territory6, 8. This is also reflected in the existence of human genetic syndromes as well as congenital or environmentally-caused human malformations featuring multiorgan phenotypes in liver, pancreas and gallbladder6, 8. Nevertheless, the precise lineage hierarchy and succession of events leading to the segregation of an endoderm progenitor compartment into hepatic, biliary, and pancreatic structures are not yet established. Here, we combine computational modelling approaches with genetic lineage tracing to assess the tissue dynamics accompanying the ontogeny of the hepato-pancreato-biliary organ system. We show that a long-term multipotent progenitor domain persists at the border between liver and pancreas, even after pancreatic fate is specified, contributing to the formation of several organ derivatives, including the liver. Moreover, using single-cell RNA sequencing we define a specialized niche that possibly supports such long-term cell fate plasticity.

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Section: Discussionsupporting

confidence: 82%