Patterning of the hepato‐pancreatobiliary boundary by BMP reveals heterogeneity within the murine liver bud

Palaria, Amrita; Angelo, Jesse R.; Guertin, Taylor M.; Mager, Jesse; Tremblay, Kimberly D.

doi:10.1002/hep.29769

Cited by 19 publications

(17 citation statements)

References 49 publications

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“…Cyp1b1 has notably strong expression in the STM, which supports liver budding [41,42]. This expression is located close to Bco1, an oxygenase that generates retinaldehyde from β-carotene.…”

Section: Do Perinatal Effects Of Cyp1b1 Deletion Arise From Expressiomentioning

confidence: 64%

“…Here, we show that Cyp1b1 is located in the STM, co-expressed with Bco1, an oxygenase that delivers retinaldehyde from β-carotene [39,40]. Liver budding has been resolved into anterior stimulation of hepatoblasts by Fgf forms, and posterior stimulation by Bmp4 from the STM [41,42].…”

Section: Introductionmentioning

confidence: 92%

“…These structures derive from cells that migrate from specific rhombomeres of the neural crest (r4 to Ba2; r5 to Ba3; r7 to Ba4). The third major site of expression is the foregut, more specifically the STM, which participates in liver bud expansion [42]. Cyp1b1 mRNA is present in caudal somites, notably with clear left/right polarization.…”

Section: Location Of Cyp1b1 At E95 In Relation To Retinoid Producingmentioning

confidence: 99%

“…Fig 5B shows the spatial relationship between Cyp1b1 and Hoxb1 in the foregut region at E9.5 in relation to Adlh1a2 and Bco1 (Figs 4B and 5A). These liver progenitor cells (hepatoblasts), which are controlled by Hnf4a [11,42,64,71], are jointly activated by Fgf forms from cardiac mesoderm and by BMP4 from the STM [25]. RA can intervene by stimulating the Hoxb1 effects on Fgf forms [35,41,42] or by enhancing Bmp4 effects [72].…”

Section: Spatial Resolution Of Cyp1b1 Cyp26c1 Hoxb1 and Pax6 In Thmentioning

confidence: 99%

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Cyp1b1 directs Srebp-mediated cholesterol and retinoid synthesis in perinatal liver; Association with retinoic acid activity during fetal development

et al. 2020

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Background Cytochrome P450 1b1 (Cyp1b1) deletion and dietary retinol deficiency during pregnancy (GVAD) affect perinatal liver functions regulated by Srebp. Cyp1b1 is not expressed in perinatal liver but appears in the E9.5 embryo, close to sites of retinoic acid (RA) signaling. Hypothesis Parallel effects of Cyp1b1 and retinol on postnatal Srebp derive from effects in the developing liver or systemic signaling. Approach Cluster postnatal increases in hepatic genes in relation to effects of GVAD or Cyp1b1 deletion. Sort expression changes in relation to genes regulated by Srebp1 and Srebp2.Test these treatments on embryos at E9.5, examining changes at the site of liver initiation. Use in situ hybridization to resolve effects on mRNA distributions of Aldh1a2 and Cyp26a1 (RA homeostasis); Hoxb1 and Pax6 (RA targets). Assess mice lacking Lrat and Rbp4 (DKO mice) that severely limits retinol supply to embryos. Results At birth, GVAD and Cyp1b1 deletion stimulate gene markers of hepatic stellate cell (HSC) activation but also suppress Hamp. These treatments then selectively prevent the postnatal onset of genes that synthesize cholesterol (Hmgcr, Sqle) and fatty acids (Fasn, Scd1), but also direct cholesterol transport (Ldlr, Pcsk9, Stard4) and retinoid synthesis (Aldh1a1, Rdh11). Extensive support by Cyp1b1 is implicated, but with distinct GVAD interventions for Srebp1 and Srebp2. At E9.5, Cyp1b1 is expressed in the septum transversum mesenchyme

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Section: Do Perinatal Effects Of Cyp1b1 Deletion Arise From Expressiomentioning

confidence: 64%

Section: Introductionmentioning

confidence: 92%

Section: Location Of Cyp1b1 At E95 In Relation To Retinoid Producingmentioning

confidence: 99%

Section: Spatial Resolution Of Cyp1b1 Cyp26c1 Hoxb1 and Pax6 In Thmentioning

confidence: 99%

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Cyp1b1 directs Srebp-mediated cholesterol and retinoid synthesis in perinatal liver; Association with retinoic acid activity during fetal development

et al. 2020

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“…Establishing a protocol to produce a single genetically labeled cell per embryo Despite in vitro evidence supporting the bi-potency of individual hepatoblasts, in vivo experiments are conspicuously absent. Furthermore, the existence of at least two spatially distinct liver bud populations with differential requirements for BMP and FGF suggest distinct hepatoblast subpopulations (Palaria et al, 2018;Wang et al, 2015). To probe this putative heterogeneity and to assess the potential of individual hepatoblasts we used an in vivo fate mapping strategy that pairs a tissue-specific TMX-inducible Cre-transgene and a lacZ reporter.…”

Section: Resultsmentioning

confidence: 99%

Single-cell murine genetic fate mapping reveals bipotential hepatoblasts and novel multi-organ endoderm progenitors

et al. 2018

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The definitive endoderm (DE) is the embryonic germ layer that forms the gut tube and associated organs, including thymus, lungs, liver and pancreas. To understand how individual DE cells furnish gut organs, genetic fate mapping was performed using the Cre-reporter paired with a tamoxifen-inducible DE-specific Cre-expressing transgene. We established a low tamoxifen dose that infrequently induced heritable expression in a single cell of individual E8.5 mouse embryos and identified clonal cell descendants at E16.5. As expected, only a fraction of the E16.5 embryos contained positive clonal descendants and a subset of these contained descendants in multiple organs, revealing novel ontogeny. Furthermore, immunohistochemical analysis was used to identify-positive hepatocytes and biliary epithelial cells, which are the cholangiocyte precursors, in each clonally populated liver. Together, these data not only uncover novel and suspected lineage relationships between DE-derived organs, but also illustrate the bipotential nature of individual hepatoblasts by demonstrating that single hepatoblasts contribute to both the hepatocyte and the cholangiocyte lineage .

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Human pancreatic progenitors

Qadir

Lanzoni

Ricordi

et al. 2020

Transplantation, Bioengineering, and Regeneration of the Endocrine Pancreas

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Patterning of the hepato‐pancreatobiliary boundary by BMP reveals heterogeneity within the murine liver bud

Cited by 19 publications

References 49 publications

Cyp1b1 directs Srebp-mediated cholesterol and retinoid synthesis in perinatal liver; Association with retinoic acid activity during fetal development

Cyp1b1 directs Srebp-mediated cholesterol and retinoid synthesis in perinatal liver; Association with retinoic acid activity during fetal development

Single-cell murine genetic fate mapping reveals bipotential hepatoblasts and novel multi-organ endoderm progenitors

Human pancreatic progenitors

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