Journal of the Pancreas Open Access

The Release of Sonic Hedgehog from Pancreatic Cancer Cells is Controlled by Cholesterol and CDON

Guner M Wahermann^* Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California, United States
^*Correspondence: Guner M Wahermann, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, United States, Email:

Received: 20-Sep-2022, Manuscript No. IPP-22-15213; Editor assigned: 22-Sep-2022, Pre QC No. IPP-22-15213(PQ); Reviewed: 07-Oct-2022, QC No. IPP-22-15213; Revised: 07-Oct-2022, Manuscript No. IPP-22-15213(R); Published: 14-Oct-2022, DOI: 10.35841/1590-8577-23.10.770

INTRODUCTION

The mammalian pancreas' function is dependent on intricate interactions between different cell types, gene expression profiles have traditionally been characterized using bulk mixtures. The transcriptomes of nearly 12,000 individual pancreatic cells from four human donors and two mouse strains were determined using a dropletbased, single-cell RNA-seq approach. All endocrine cell types, including uncommon epsilon-cells; exocrine cell types; vascular cells; Schwann cells; quiescent and active stellate cells; and four types of immune cells could be grouped into 15 clusters that matched previously defined cell categories. We discovered ductal cell subpopulations with unique expression profiles and confirmed their presence using immunohistochemistry staining. Furthermore, we discovered variability in the regulation of genes related to functional maturation and levels of cholesterol in human beta-cells [1].

Finally, we used single-cell data to deconvolve bulk gene expression collections in order to uncover diseaseassociated differential expression. Our database can be used to find new cell type-specific transcription factors, signaling receptors, and medically significant genes [1].

Drainage of the pseudocyst is the most appropriate treatment for gigantic pancreatic pseudocysts due to their huge size. The goal of draining pseudocysts can be accomplished through a variety of therapy techniques. An endoscopic ultrasound-guided cystogastrostomy is one of the most regularly used procedures, and this case demonstrates it as a viable therapeutic choice for big pancreatic pseudocyst [2].

Organogenesis' complexity makes in vitro creation of organs from a patient's Pluripotent Stem Cells (PSCs) difficult, which is the ultimate goal of regenerative medicine. PSCs implanted into Pdx1(-/-) (pancreatogenesisdisabled) mouse blastocysts developmentally compensated for the loss of the pancreatic "developmental niche," resulting in a pancreas made virtually exclusively of PSCs. We injected mouse or rat PSCs into rat or mouse blastocysts, respectively, to test the potential for xenogeneic techniques in blastocyst complementation. This resulted in interspecific chimaeras, showing that PSCs can contribute to xenogeneic development between mouse and rat. The body size and species-specific organogenesis of these mouse/rat chimaeras were predominantly controlled by the host blastocyst and/or foster mother. We next implanted rat wild-type PSCs into Pdx1(-/-) mouse blastocysts, resulting in mice with a fully functional rat pancreas. These findings demonstrate the feasibility of interspecific blastocyst complementation and the in vivo creation of organs from donor PSCs in a xenogeneic environment [3].

We employed iterative weighted gene correlation network analysis to create a gene co-expression network (GCN) from 11 temporally and genetically characterized mouse cell populations to gain a better understanding of pancreatic-cell development. The GCN was then used to gain three new biological insights, as it had 91 unique modules. First, we discovered that during pancreas development, the clustered protocadherin genes are differently expressed. Pcdhy genes are expressed preferentially in pancreatic endoderm, nascent islets, and mature -cells. Second, we discovered 81 Zinc Finger Protein (ZFP) genes that are selectively expressed throughout endocrine specification and -cell maturation after identifying sub-networks of transcriptional regulators for each embryonic stage. Finally, we used the GCN to pick three ZFPs for future investigation using CRISPR mutagenesis in mice. There were fewer pancreatic endocrine cells, changes in exocrine cell shape, and significant changes in gene expression in the pancreas implicated in protein translation, hormone secretion, and developmental pathways. Our findings suggest that developmentally orientated GCNs could be useful for learning more about gene control throughout organogenesis [4].

Important events in the organogenesis of the mouse pancreas have been defined thanks to extensive research. These findings were used to create Human Embryonic Stem Cell (hESC) differentiation methods with the goal of producing functional glucose-responsive, insulinproducing human cells. Despite significant advancements in hESC differentiation, existing mouse developmental biology-based procedures can only create human -cells in vivo. New differentiation markers and recently developed reagents may offer a once-in-a-lifetime opportunity to create a high-density expression map of human foetal pancreas and pancreatic islets, which might be used as a reference point for in vitro hESC differentiation [5].

Conclusion

In rodent models of diabetes mellitus, somatostatin secretion is disrupted, which might explain the absence of adequate hypoglycemia-induced glucagon secretion, a deficiency that could be reduced by somatostatin receptor 2 antagonists. As an adjuvant to insulin treatment, somatostatin antagonists or medicines that reduce somatostatin production have been proposed. We outline the cell physiology of somatostatin secretion, what can go wrong in diabetes mellitus, and the therapeutic potential of medicines targeting somatostatin secretion or activity in this Review. We consider the pathophysiology of insulin secretion by considering the properties of human pancreatic cells: their glucose sensing, the ion channel complement underlying glucose-induced electrical activity that culminates in exocytosis release of insulin, the cellular control of exocytosis, and the modulation of insulin secretion by circulating hormones and locally released neurotransmitters.

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