Single-cell transcriptome analysis for cancer and biology of the pancreas: A review on recent progress

Abstract

Single-cell sequencing has become one of the most used techniques across the wide field of biology. It has enabled researchers to investigate the whole transcriptome at the cellular level across tissues, which unlocks numerous potentials for basic and applied studies in future diagnosis and therapy. Here, we review the impact of single-cell RNA sequencing, as the prominent single-cell technique, in pancreatic biology and cancer. We discuss the most recent findings about pancreatic physiology and pathophysiology owing to this technological advancement in the past few years. Using single-cell RNA sequencing, researchers have been able to discover cellular heterogeneity across healthy cell types, as well as cancer tissues of the pancreas. We will discuss the new immunological targets and new molecular mechanisms of progression in the microenvironment of pancreatic cancer studied using single-cell RNA sequencing. The scope is not limited to cancer tissues, and we cover novel developmental, evolutionary, physiological, and heterogenic insights that have also been achieved recently for pancreatic tissues. We cover all biological insights derived from the single-cell RNA sequencing data, discuss the corresponding pros and cons, and finally, conclude how future research can move better by utilizing single-cell analysis for pancreatic biology.

Keywords: genetic heterogeneity; pancreas biology; pancreas cancer; single-cell sequencing; transcriptome analysis.

FIGURE 1

Three main biomolecular areas covered by single-cell analysis (in light blue), as well as the techniques incorporated (in the rectangular box).

FIGURE 2

Illustration of how sequencing and CRISPR can be used in combination to further improve human knowledge on various biological functions.

FIGURE 3

Characterizing all the immune cells in the pancreatic tumor microenvironment (Tang et al., 2021).

FIGURE 4

Carstens et al. (2021) provided evidence on how an epithelial phenotype of the primary tumors promotes metastasis and inhibits immune responses; they classified the primary tumors using single-cell RNA-seq.

FIGURE 5

Identification of tissue composition at a molecular level (Hosein et al., 2019). (A) Cell populations in normal, early, and late cancerous tissue; (B) comparison in between two subtypes of KRAS-induced cancer; (C) fibroblasts into prospective in normal tissues as well as early and late cancer tissue,; and (D) populations of macrophages in magnification through the cancer course.

FIGURE 6

Efforts to characterize and subtype the pancreatic tissue. Comparing the percentages for each subpopulation of the pancreatic tissue under normal and disease conditions using sequencing technology has been the method of diagnosis for several groups. Baron et al. (2016)conducted a descriptive study on pancreatic cellular subtypes, and Wollny et al. (2016) shed light more on one subtype, namely, the diabetically prominent islets.

FIGURE 7

Effort to isolate and characterize human stem cells. The embryonic and adult stem cells have been characterized owing to single-cell RNA sequencing which now provides a substrate to look deeper for underlying mechanisms. (A) Wiedenmann et al. used microfluidic technology to grow duct-like organoids from pancreatic progenitors (Wiedenmann et al., 2021). (B) Mameishvili et al. provided evidence that ALD1HB1 is the selector gene for pancreatic adult progenitors and is associated with KRAS-driven pancreatic cancer.