A Specialized Niche in the Pancreatic Microenvironment Promotes Endocrine Differentiation

Cozzitorto, Corinna; Mueller, Laura; Ruzittu, Silvia; Mah, Nancy; Willnow, David; Darrigrand, Jean Francois; Wilson, Heather M.; Khosravinia, Daniel; Mahmoud, Amir Ala; Risolino, Maurizio; Selleri, Licia; Spagnoli, Francesca

doi:10.1016/j.devcel.2020.08.003

Cited by 40 publications

(42 citation statements)

References 57 publications

(80 reference statements)

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“…For example, mesenchyme was shown to be required for pancreas development as long ago as the 1960s ( Golosow and Grobstein, 1962 ). More recently, the use of sophisticated transgenic mouse models has made it possible to separate out the various developmental roles of the mesenchyme at different timepoints ( Landsman et al, 2011 ) and to identify mesenchyme subpopulations with different pro-endocrine potentials ( Cozzitorto et al, 2020 ). Mesenchymal niche-derived factors are beneficial for hPSC differentiation into pancreatic endocrine cells ( Guo et al, 2013 ; Russ et al, 2016 ; Mamidi et al, 2018 ; Cozzitorto et al, 2020 ).…”

Section: Novel Insight Into Endocrine Pancreas Development From Single-cell Rna-seqmentioning

confidence: 99%

Endocrine Pancreas Development and Dysfunction Through the Lens of Single-Cell RNA-Sequencing

Szlachcic

Ziojla

Kizewska

et al. 2021

Front. Cell Dev. Biol.

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A chronic inability to maintain blood glucose homeostasis leads to diabetes, which can damage multiple organs. The pancreatic islets regulate blood glucose levels through the coordinated action of islet cell-secreted hormones, with the insulin released by β-cells playing a crucial role in this process. Diabetes is caused by insufficient insulin secretion due to β-cell loss, or a pancreatic dysfunction. The restoration of a functional β-cell mass might, therefore, offer a cure. To this end, major efforts are underway to generate human β-cells de novo, in vitro, or in vivo. The efficient generation of functional β-cells requires a comprehensive knowledge of pancreas development, including the mechanisms driving cell fate decisions or endocrine cell maturation. Rapid progress in single-cell RNA sequencing (scRNA-Seq) technologies has brought a new dimension to pancreas development research. These methods can capture the transcriptomes of thousands of individual cells, including rare cell types, subtypes, and transient states. With such massive datasets, it is possible to infer the developmental trajectories of cell transitions and gene regulatory pathways. Here, we summarize recent advances in our understanding of endocrine pancreas development and function from scRNA-Seq studies on developing and adult pancreas and human endocrine differentiation models. We also discuss recent scRNA-Seq findings for the pathological pancreas in diabetes, and their implications for better treatment.

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Section: Novel Insight Into Endocrine Pancreas Development From Single-cell Rna-seqmentioning

confidence: 99%

Endocrine Pancreas Development and Dysfunction Through the Lens of Single-Cell RNA-Sequencing

Szlachcic

Ziojla

Kizewska

et al. 2021

Front. Cell Dev. Biol.

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“…As a proof-ofconcept, here we exemplified how to extract information on the 3D tissue architecture as well as the relative position of epithelial, mesenchymal, and endothelial cells from LSFM images of the developing pancreas. These data provide us with novel ways to visualize the intimate interaction between epithelial cells and Nkx2.5 + mesenchymal cells, which contribute to the proper development of the endocrine pancreas (Cozzitorto et al, 2020). Furthermore, we applied our analysis pipelines to gain insights into the cell ratio between epithelial, mesenchymal, and endothelial cells at key time points during pancreas development.…”

Section: Discussionmentioning

confidence: 99%

“…5), which does not exclude the presence of other cell types, such as neuronal, lymphatic, or immune cells, in this fraction. However, these cell populations are rare within the pancreatic tissue at E12.5 and E14.5 (Burris and Hebrok, 2007;Cozzitorto et al, 2020) (Fig. S2), especially within the 15 µm radius from the epithelium, being therefore negligible in the calculation of relative cell abundance.…”

Section: D Image Analyses Allow Precise Quantification Of Cell Type Abundancementioning

confidence: 99%

Development of a 3D atlas of the embryonic pancreas for topological and quantitative analysis of heterologous cell interactions

Glorieux

Sapala

Willnow

et al. 2021

Preprint

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Generating comprehensive image maps, while preserving spatial 3D context, is essential to quantitatively assess and locate specific cellular features and cell-cell interactions during organ development. Despite the recent advances in 3D imaging approaches, our current knowledge of the spatial organization of distinct cell types in the embryonic pancreatic tissue is still largely based on 2D histological sections. Here, we present a light-sheet fluorescence microscopy approach to image the pancreas in 3D and map tissue interactions at key development time points in the mouse embryo. We used transgenic mouse models and antibodies to visualize the three main cellular components within the developing pancreas, including epithelial, mesenchymal and endothelial cell populations. We demonstrated the utility of the approach by providing volumetric data, 3D distribution of distinct progenitor populations and quantification of relative cellular abundance within the tissue. Lastly, our image data were combined in an open source online repository (referred to as Pancreas Embryonic Cell Atlas). This image dataset will serve the scientific community by enabling further investigation on pancreas organogenesis but also for devising strategies for the in vitro generation of transplantable pancreatic tissue for regenerative therapies.

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Section: The Protective Effects Of Va On the Pancreasmentioning

confidence: 99%

“…The interactions of mesenchymal-epithelial cells are necessary for proper maturation of tissues ( 55 – 57 ). Studies have indicated that the pancreatic mesenchyme not only influences the expansion of early pancreatic progenitors but also regulates the proliferation of terminally differentiated endocrine cells during the final phase of gestation ( 57 ). Moreover, PSCs are important mesenchymal supporting cells that can maintain the normal basement membrane to stabilize the cell cytoskeleton and structure, thereby protecting the normal function of parenchymal cells ( 58 ).…”

Section: The Protective Effects Of Va On the Pancreasmentioning

confidence: 99%

Vitamin A and Its Multi-Effects on Pancreas: Recent Advances and Prospects

et al. 2021

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Vitamin A (VA), which is stored in several forms in most tissues, is required to maintain metabolite homeostasis and other processes, including the visual cycle, energy balance, epithelial cell integrity, and infection resistance. In recent years, VA molecules, also known as retinoids, have been extensively explored and used in the treatment of skin disorders and immune-related tumors. To date, several observational and interventional studies have explored the relationship between VA status and the pathogenesis of diabetes. In particular, VA micronutrients have been shown to regulate pancreatic development, β-cell function, pancreatic innate immune responses, and pancreatic stellate cells phenotypes through multiple mechanisms. However, there are still many problems to be proven or resolved. In this review, we summarize and discuss recent and available evidence on VA biological metabolism in the pancreas. Analysis of the effects of VA on metabolism in the pancreas will contribute to our understanding of the supportive physiological roles of VA in pancreas protection.

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A Specialized Niche in the Pancreatic Microenvironment Promotes Endocrine Differentiation

Cited by 40 publications

References 57 publications

Endocrine Pancreas Development and Dysfunction Through the Lens of Single-Cell RNA-Sequencing

Endocrine Pancreas Development and Dysfunction Through the Lens of Single-Cell RNA-Sequencing

Development of a 3D atlas of the embryonic pancreas for topological and quantitative analysis of heterologous cell interactions

Vitamin A and Its Multi-Effects on Pancreas: Recent Advances and Prospects

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