Gastroenterology: How pancreatic injury causes cancer to form

Researchers from Vanderbilt University and the Salk Institute for Biological Research in the United States have recently discovered through single-cell transcriptomics analysis that acinar cells in the pancreas can form new cell types to reduce damage, but they are more likely to be in the presence of mutations.
Carcinogenesis occurs
.

The research was published in the journal Gastroenterology on October 22 and was led by assistant professor Kathy DelGiorno at Vanderbilt University and Geoffrey Wahl, professor at the Salk Institute
.

It helps people understand the mechanisms of pancreatic injury, regeneration and tumor formation

Pancreatic cancer is one of the common malignant tumors of the digestive tract, and the incidence rate continues to rise worldwide
.

The five-year survival rate after diagnosis of pancreatic cancer is only 10%, and it is one of the worst-prognostic malignant tumors, so it is also known as the "king of cancer"

Previous studies have found that if pancreatic cells are damaged, the process of acinar-ductal metaplasia (ADM) occurs, that is to say, acinar cells have various characteristics of ductal cells
.

In this case, if the cell unfortunately carries the Kras mutation, it is possible to acquire the characteristics of pancreatic ductal adenocarcinoma (PDAC)

In this study, the researchers hope to use a variety of studies to determine the cell types formed after pancreatic injury, transcription changes, and markers of disease progression
.

Researchers use enhanced yellow fluorescent protein (EYFP) to trace the lineage of acinar cells to understand their fate after injury
.

After that, single-cell RNA sequencing (scRNA-seq) was used to determine the transcripts of more than 13,000 EYFP+ cells and generate developmental trajectories

The results of sequencing analysis showed that under chronically injured conditions, acinar cell metaplasia became a mucinous progenitor cell-like population, similar to gastric pyloric metaplasia
.

The lineage trajectory indicates that this progenitor-like population can produce tuft cells and enteroendocrine cells (ECC)

The researchers believe that the results of this study support the long-standing view that tissue inflammation causes cells to reprogram to a more primitive state that is developmentally plastic, which helps tissue repair under normal conditions
.

However, when the Kras gene is mutated, it may cause a malignant tumor with a very poor prognosis

The first author of the article, Zhibo Ma of the Salk Institute for Biological Research, said: "Our work has captured with unprecedented resolution how these acinar cells change in response to damage
.

We were able to identify a variety of acinar cells produced Different cells and reveal their source

In the next step, they will use genetically modified models to study the lineage trajectory and functional role of the newly discovered cell types
.
"We will determine the role of these cell types in pancreatic injury, regeneration and tumorigenesis," DelGiorno said
.

Original Search

Zhibo Ma, Nikki K.
Lytle, et al.
Single-cell transcriptomics reveals a conserved metaplasia program in pancreatic injury.
Gastroenterology, 2021; DOI: 10.
1053/j.
gastro.
2021.
10.
027