Pancreatic Inflammation Redirects Acinar to β Cell Reprogramming

Clayton, Hannah W.; Osipovich, Anna B.; Stancill, Jennifer S.; Schneider, Judsen; Vianna, Pedro G.; Shanks, Carolyn M.; Yuan, Weiping; Gu, Guoqiang; Manduchi, Elisabetta; Stoeckert, Christian J.; Magnuson, Mark A.

doi:10.1016/j.celrep.2016.10.068

Cited by 27 publications

(14 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The source of new cells that contribute to the expansion of adult β cell mass during adaptive processes has been debated for several years. Although in vitro and in vivo experiments suggest acinar cells can be converted into β-like cells (19)(20)(21), lineage trace experiments did not support this hypothesis in vivo (22). Adult ductal cells have been suggested to act as precursors of β cells because embryonic ducts are direct precursors of neurogenin 3 + (NGN3 + ) cells, which can give rise to all pancreatic endocrine cells (23).…”

Section: Introductionmentioning

confidence: 99%

Human duct cells contribute to β cell compensation in insulin resistance

Dirice¹,

Jesus²,

Kahraman³

et al. 2019

JCI Insight

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 99%

Human duct cells contribute to β cell compensation in insulin resistance

Dirice¹,

Jesus²,

Kahraman³

et al. 2019

JCI Insight

View full text Add to dashboard Cite

“…Thus, Pan et al (2013) showed the ability of acinar-to-beta-cell conversion, including an intermediate step with pancreatic multipotent progenitor cells. Clayton et al (2016) performed direct reprogramming of acinar cells on a transgenic mouse by the virus-based induction of PDX1, MAFA, and NGN3. Another important output from their study concerns the impact of inflammation on the reprogramming result.…”

Section: Hb9mentioning

confidence: 99%

Advances and complications of regenerative medicine in diabetes therapy

Brovkina

Дашинимаев

2020

PeerJ

View full text Add to dashboard Cite

The rapid development of technologies in regenerative medicine indicates clearly that their common application is not a matter of if, but of when. However, the regeneration of beta-cells for diabetes patients remains a complex challenge due to the plurality of related problems. Indeed, the generation of beta-cells masses expressing marker genes is only a first step, with maintaining permanent insulin secretion, their protection from the immune system and avoiding pathological modifications in the genome being the necessary next developments. The prospects of regenerative medicine in diabetes therapy were promoted by the emergence of promising results with embryonic stem cells (ESCs). Their pluripotency and proliferation in an undifferentiated state during culture have ensured the success of ESCs in regenerative medicine. The discovery of induced pluripotent stem cells (iPSCs) derived from the patients’ own mesenchymal cells has provided further hope for diabetes treatment. Nonetheless, the use of stem cells has significant limitations related to the pluripotent stage, such as the risk of development of teratomas. Thus, the direct conversion of mature cells into beta-cells could address this issue. Recent studies have shown the possibility of such transdifferentiation and have set trends for regeneration medicine, directed at minimizing genome modifications and invasive procedures. In this review, we will discuss the published results of beta-cell regeneration and the advantages and disadvantages illustrated by these experiments.

show abstract

“…Proliferative or progenitor-like exocrine cells also may provide clues on regeneration mechanisms in endocrine cells since they are derived from a common progenitor. Furthermore, recent evidence indicates that acinar reprogramming efficiency is significantly reduced upon pancreatic inflammation or hyperglycemia but improved by inhibition of contact-mediated signaling [125] , [130] , [131] , [132] . This highlights the importance of investigating extrinsic factors that potentially hamper or enhance cell conversion in vivo .…”

Section: Approaches Of Endogenous β-Cell Regenerationmentioning

confidence: 99%

Systematic single-cell analysis provides new insights into heterogeneity and plasticity of the pancreas

Tritschler

Theis

Lickert

et al. 2017

Molecular Metabolism

103

View full text Add to dashboard Cite

BackgroundDiabetes mellitus is characterized by loss or dysfunction of insulin-producing β-cells in the pancreas, resulting in failure of blood glucose regulation and devastating secondary complications. Thus, β-cells are currently the prime target for cell-replacement and regenerative therapy. Triggering endogenous repair is a promising strategy to restore β-cell mass and normoglycemia in diabetic patients. Potential strategies include targeting specific β-cell subpopulations to increase proliferation or maturation. Alternatively, transdifferentiation of pancreatic islet cells (e.g. α- or δ-cells), extra-islet cells (acinar and ductal cells), hepatocytes, or intestinal cells into insulin-producing cells might improve glycemic control. To this end, it is crucial to systematically characterize and unravel the transcriptional program of all pancreatic cell types at the molecular level in homeostasis and disease. Furthermore, it is necessary to better determine the underlying mechanisms of β-cell maturation, maintenance, and dysfunction in diabetes, to identify and molecularly profile endocrine subpopulations with regenerative potential, and to translate the findings from mice to man. Recent approaches in single-cell biology started to illuminate heterogeneity and plasticity in the pancreas that might be targeted for β-cell regeneration in diabetic patients.Scope of reviewThis review discusses recent literature on single-cell analysis including single-cell RNA sequencing, single-cell mass cytometry, and flow cytometry of pancreatic cell types in the context of mechanisms of endogenous β-cell regeneration. We discuss new findings on the regulation of postnatal β-cell proliferation and maturation. We highlight how single-cell analysis recapitulates described principles of functional β-cell heterogeneity in animal models and adds new knowledge on the extent of β-cell heterogeneity in humans as well as its role in homeostasis and disease. Furthermore, we summarize the findings on cell subpopulations with regenerative potential that might enable the formation of new β-cells in diseased state. Finally, we review new data on the transcriptional program and function of rare pancreatic cell types and their implication in diabetes.Major conclusionNovel, single-cell technologies offer high molecular resolution of cellular heterogeneity within the pancreas and provide information on processes and factors that govern β-cell homeostasis, proliferation, and maturation. Eventually, these technologies might lead to the characterization of cells with regenerative potential and unravel disease-associated changes in gene expression to identify cellular and molecular targets for therapy.

show abstract

Pancreatic Inflammation Redirects Acinar to β Cell Reprogramming

Cited by 27 publications

References 49 publications

Human duct cells contribute to β cell compensation in insulin resistance

Human duct cells contribute to β cell compensation in insulin resistance

Advances and complications of regenerative medicine in diabetes therapy

Systematic single-cell analysis provides new insights into heterogeneity and plasticity of the pancreas

Contact Info

Product

Resources

About