Adult human pancreatic acinar cells dedifferentiate into an embryonic progenitor-like state in 3D suspension culture

Baldan, Jonathan; Houbracken, Isabelle; Rooman, Ilse; Bouwens, Luc

doi:10.1038/s41598-019-40481-1

Cited by 31 publications

(34 citation statements)

References 34 publications

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“…Another path involves acinar re-programing and trans-differentiation leading to acini-duct metaplasias (ADM) [ 34 , 35 , 36 ]. Both PanIN and ADM processes may be in parallel or in tandem and there might be differences between rodents and humans [ 37 , 38 ].…”

Section: Pancreatic Cancer and Its Tumor Microenvironmentmentioning

confidence: 99%

Purinergic Signaling in Pancreas—From Physiology to Therapeutic Strategies in Pancreatic Cancer

Novak¹,

Yu²,

Magni³

et al. 2020

IJMS

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The purinergic signaling has an important role in regulating pancreatic exocrine secretion. The exocrine pancreas is also a site of one of the most serious cancer forms, the pancreatic ductal adenocarcinoma (PDAC). Here, we explore how the network of purinergic and adenosine receptors, as well as ecto-nucleotidases regulate normal pancreatic cells and various cells within the pancreatic tumor microenvironment. In particular, we focus on the P2X7 receptor, P2Y2 and P2Y12 receptors, as well as A2 receptors and ecto-nucleotidases CD39 and CD73. Recent studies indicate that targeting one or more of these candidates could present new therapeutic approaches to treat pancreatic cancer. In pancreatic cancer, as much as possible of normal pancreatic function should be preserved, and therefore physiology of purinergic signaling in pancreas needs to be considered.

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Section: Pancreatic Cancer and Its Tumor Microenvironmentmentioning

confidence: 99%

Purinergic Signaling in Pancreas—From Physiology to Therapeutic Strategies in Pancreatic Cancer

Novak¹,

Yu²,

Magni³

et al. 2020

IJMS

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“…The analysis reveals that 444 genes are differentially expressed (p < 0.001), among which we also find biomarkers for the two cell-types (Figure 4(b)-bottom, Figure S1, Supplementary Excel File). Specifically, KRT19, a positive biomarker gene 36 for Ductal cell-type, is significantly underexpressed on the misclassified group and CTRC, a positive biomarker for Acinar cells 36 , is differentially expressed but with a very low expression pattern. These findings suggest that the Ductal cells classified as Acinar are indeed not Ductal, and that further analysis is needed to confirm their true identity.…”

Section: Jind+ Misclassified Cells Exhibit Differentially Expressed Gmentioning

confidence: 99%

JIND: Joint Integration and Discrimination for Automated Single-Cell Annotation

Goyal

Serrano

Shomorony

et al. 2020

Preprint

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Single-cell RNA-seq is a powerful tool in the study of the cellular composition of different tissues and organisms. A key step in the analysis pipeline is the annotation of cell-types based on the expression of specific marker genes. Since manual annotation is labor-intensive and does not scale to large datasets, several methods for automated cell-type annotation have been proposed based on supervised learning. However, these methods generally require feature extraction and batch alignment prior to classification, and their performance may become unreliable in the presence of cell-types with very similar transcriptomic profiles, such as differentiating cells. We propose JIND, a framework for automated cell-type identification based on neural networks that directly learns a low-dimensional representation (latent code) in which cell-types can be reliably determined. To account for batch effects, JIND performs a novel asymmetric alignment in which the transcriptomic profile of unseen cells is mapped onto the previously learned latent space, hence avoiding the need of retraining the model whenever a new dataset becomes available. JIND also learns cell-type-specific confidence thresholds to identify and reject cells that cannot be reliably classified. We show on datasets with and without batch effects that JIND classifies cells more accurately than previously proposed methods while rejecting only a small proportion of cells. Moreover, JIND batch alignment is parallelizable, being more than five or six times faster than Seurat integration. Availability: https://github.com/mohit1997/JIND.

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“…These organoids showed the characteristics of ductal cells and a strong proliferative capacity. In addition, one group reported that acinar cells could be dedifferentiated into progenitor-like cells by 3D suspension culture ( Baldan et al, 2019 ). However, whether these progenitor-like cells can be differentiated back into acinar cells remains unclear.…”

Section: Current Organoid Technologiesmentioning

confidence: 99%

Organoid technology for tissue engineering

Zhang

Xia

et al. 2020

Journal of Molecular Cell Biology

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For centuries, the attempts have been continuously made to artificially reconstitute counterparts of the in vivo organs from their tissues or cells. Only in the recent decade has organoid technology as a whole technological field systematically emerged and been shown to play important roles in tissue engineering. Based on their self-organizing capacities, stem cells of versatile organs, both harvested and induced, can form 3D structures that are structurally and functionally similar to their in vivo counterparts. These organoid models provide a powerful platform for elucidating the development mechanisms, modeling diseases, and screening drug candidates. In this review, we will summarize the advances of this technology for generating various organoids of tissues from the three germ layers and discuss their drawbacks and prospects for tissue engineering.

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Adult human pancreatic acinar cells dedifferentiate into an embryonic progenitor-like state in 3D suspension culture

Cited by 31 publications

References 34 publications

Purinergic Signaling in Pancreas—From Physiology to Therapeutic Strategies in Pancreatic Cancer

Purinergic Signaling in Pancreas—From Physiology to Therapeutic Strategies in Pancreatic Cancer

JIND: Joint Integration and Discrimination for Automated Single-Cell Annotation

Organoid technology for tissue engineering

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