Quantitative lineage analysis identifies a hepato-pancreato-biliary progenitor niche

Willnow, David; Benary, Uwe; Margineanu, Anca; Vignola, Maria Lillina; Konrath, Fabian; Pongrac, I; Karimaddini, Zahra; Vigilante, Alessandra; Wolf, Jana; Spagnoli, Francesca M.

doi:10.1038/s41586-021-03844-1

Cited by 29 publications

(20 citation statements)

References 61 publications

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“…4c, d). They displayed different expression patterns from liver hepatocytes, and showed high expression of early hepatic stem or progenitor marker Hnf4a 23,24 (Extended Data Fig. 4e, f).…”

Section: Cellular Changes During the Mouse Developmentmentioning

confidence: 99%

Systematic identification of cell-fate regulatory programs using a single-cell atlas of mouse development

Fei

Chen

et al. 2022

Nat Genet

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Waddington's epigenetic landscape is an abstract metaphor frequently used to explain cell fate decisions. Recent advances in single-cell genomics are altering our understanding of the Waddington landscape. Yet, the molecular regulations behind remain poorly understood. We construct a dynamic cell landscape of mouse lineage differentiation at the single-cell level and thereby reveal both lineage-common and lineage-specific regulatory programs during cell type maturation. We verify lineage-common regulatory programs that are universal during the development of invertebrates and vertebrates. In particular, we identify Xbp1 as an evolutionarily conserved regulator of cell fate determinations across different species. We demonstrate that Xbp1 transcriptional regulation is important for the stabilization of the genetic network for a wide range of cell types. Our results offer genetic and molecular insights into the gene regulatory programs systematically and provide resources to advance the understanding of the cell fate decisions.

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“…4c, d). They displayed different expression patterns from liver hepatocytes, and showed high expression of early hepatic stem or progenitor marker Hnf4a 23,24 (Extended Data Fig. 4e, f).…”

Section: Cellular Changes During the Mouse Developmentmentioning

confidence: 99%

Systematic identification of cell-fate regulatory programs using a single-cell atlas of mouse development

Fei

Chen

et al. 2022

Nat Genet

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“…Willnow et al showed that quantitative measurement of the rudiment size by Cre-loxP labeling found that the size of liver bud increased faster than the pancreato-biliary bud, and this phenomenon was not due to different proliferation activities. Using a mathematical simulation on a cell plasticity model, they suggested the existence of a population of multipotent progenitors that could generate both liver progenitors and pancreato-biliary progenitors, which was confirmed by further lineage tracing experiments (Willnow et al, 2021 ). Of note, few of the above statistical models or mathematical models on cell fate decisions are built based on SCLT data.…”

Section: Current and Promising Applications Of Scltmentioning

confidence: 84%

Connecting past and present: single-cell lineage tracing

2022

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Central to the core principle of cell theory, depicting cells’ history, state and fate is a fundamental goal in modern biology. By leveraging clonal analysis and single-cell RNA-seq technologies, single-cell lineage tracing provides new opportunities to interrogate both cell states and lineage histories. During the past few years, many strategies to achieve lineage tracing at single-cell resolution have been developed, and three of them (integration barcodes, polylox barcodes, and CRISPR barcodes) are noteworthy as they are amenable in experimentally tractable systems. Although the above strategies have been demonstrated in animal development and stem cell research, much care and effort are still required to implement these methods. Here we review the development of single-cell lineage tracing, major characteristics of the cell barcoding strategies, applications, as well as technical considerations and limitations, providing a guide to choose or improve the single-cell barcoding lineage tracing.

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“…Embryonic explants from this region appear to contain multi-potent progenitors, but in the absence of exogenous signalling default to pancreas differentiation ex vivo 7 . However, in vivo , VFG progenitors and their descendants retain multi-potency up to E11.5 in mouse at the base of the three VFG organs 9 . As the location of these progenitor cells is close to both the cardiac mesoderm (FGF source) and septum transversum mesenchyme (BMP source), both components in VFG culture media, it is possible that these founder populations persist via self-renewing cell division in the embryo and that their proliferation may be required for efficient onward differentiation.…”

Section: Discussionmentioning

confidence: 99%

“…As the location of these progenitor cells is close to both the cardiac mesoderm (FGF source) and septum transversum mesenchyme (BMP source), both components in VFG culture media, it is possible that these founder populations persist via self-renewing cell division in the embryo and that their proliferation may be required for efficient onward differentiation. How many rounds of proliferation are required in these lineage-restricted progenitors to insure high fidelity differentiation is hard to approximate, although the cell cycle length in the foregut endoderm has been estimated based on BrdU labelling as 17.3-26.6 hours depending on the precise location of the progenitor cells 9 . Proliferation in this region in vivo is dependent on the homeobox HHEX 22 , similar to the phenotype we observe in response to knocking this factor down in VFG.…”

Section: Discussionmentioning

confidence: 99%

“…ADE is formed as a result of the anterior migration of cells from the anterior region of the primitive streak at the beginning of gastrulation. The anterior-most DE will then migrate ventrally to form the ventral foregut, containing a bipotent precursor of liver and ventral pancreas 7, 8 , a population that has recently been shown to expand and retain potency for both lineages in vivo over a period of several days of mouse development 9 .…”

Section: Introductionmentioning

confidence: 99%

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Expansion of Ventral Foregut Primes the Enhancer Landscape for Organ Specific Differentiation

Wong

Kumar

Proks

et al. 2022

Preprint

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Cell proliferation is fundamental for almost all stages of development and differentiation that require an increase cell number. Although cell cycle phase has been associated with differentiation, the actual process of proliferation is not seen as having a specific role. Here we exploit human embryonic stem cell derived endodermal progenitors that we find are an in vitro model for the ventral foregut. These cells exhibit expansion dependent increases in differentiation efficiency to pancreatic progenitors that are linked to organ-specific enhancer priming at the level of chromatin accessibility and the decommissioning of lineage inappropriate enhancers. Our findings suggest that cell proliferation in embryonic development is about more than tissue expansion, it is required to ensure equilibration of gene regulatory networks allowing cells to become primed for future differentiation. The use of expansion of lineage specific intermediates may therefore be an important step in high fidelity in vitro differentiation.

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Quantitative lineage analysis identifies a hepato-pancreato-biliary progenitor niche

Cited by 29 publications

References 61 publications

Systematic identification of cell-fate regulatory programs using a single-cell atlas of mouse development

Systematic identification of cell-fate regulatory programs using a single-cell atlas of mouse development

Connecting past and present: single-cell lineage tracing

Expansion of Ventral Foregut Primes the Enhancer Landscape for Organ Specific Differentiation

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