Basal progenitor cells bridge the development, malignant cancers, and multiple diseases of esophagus

Lin, Baoshun; Xie, Fuan; Xiao, Zhangwu; Hong, Xiaoqian; Tian, Liming; Liu, Kuancan

doi:10.1002/jcp.26136

Cited by 4 publications

(5 citation statements)

References 84 publications

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“…Adult stem cells are vital for tissue/organ maintenance. Two models, the homogeneity and heterogeneity models, have been proposed for self-renewal and maintenance of the tissue homeostasis of the mature stratified squamous esophageal epithelium ( Zhang et al, 2017 , 2021 ; Lin et al, 2018 ). The homogeneity model hypothesizes that cells in the basal layer consist of one single population that can function as stem-like progenitors via the cell division cycle to produce daughter cells.…”

Section: Introductionmentioning

confidence: 99%

Identification and characterization of stem cells in mammalian esophageal stratified squamous epithelia

Yang

Deng

Qiao

et al. 2022

Journal of Molecular Cell Biology

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Somatic stem cells are essential for the maintenance of tissue homeostasis. Despite its importance, how the esophageal stratified squamous epithelium executes its self-renewal and maintenance remains elusive. In this study, using 5-bromo-2'-deoxyuridine (BrdU) label-chase in rats in vivo and rat esophageal organoids in vitro together with genome-wide DNA methylation and single-cell RNA sequencing, we identified a slow-cycling/quiescent stem cell population that contained high levels of hemidesmosomes (HDs) and low levels of Wnt signaling localized spatially and randomly at the basal layer of the esophageal epithelium. Pseudotime cell trajectory analysis indicated that tissue cells originated from quiescent basal stem cells in the basal layer. Perturbations of HD component expression and/or Wnt signaling reduced the stem cell population in the basal layer of esophageal keratinocyte organoids, resulting in alterations in the organoid formation rate, size, morphogenesis, and proliferation–differentiation homeostasis. Furthermore, not only high levels of HDs and low levels of Wnt signaling but also an interplay between HD and Wnt signaling defined the stem cells of the basal layer. Hence, HDs and Wnt signaling are critical determinants for defining the stem cells of the basal layer required for tissue homeostasis in mammalian esophagi.

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Section: Introductionmentioning

confidence: 99%

Identification and characterization of stem cells in mammalian esophageal stratified squamous epithelia

Yang

Deng

Qiao

et al. 2022

Journal of Molecular Cell Biology

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“…Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal cancer in Asian countries and it is ranked as the sixth leading cause of cancer death globally [17]. EAC is more prominent in the western world and is linked to obesity [18,19]. The most established risk factors for EC are smoking, alcohol and reflux esophagitis, however, they are not the only contributors [20].…”

Section: Introduction To Esophageal Cancermentioning

confidence: 99%

“…There are several theories as to how this occurs which is explained in more detail in Figure 2A. The most current theory involves abnormal differentiation of gastric cardia progenitor cells that migrate into the distal esophagus [19,22]. The reversion to simple columnar epithelium makes the esophagus more resistant to chronic inflammation due to acid-peptic damage [19].…”

Section: Introduction To Esophageal Cancermentioning

confidence: 99%

“…Once Barrett's esophagus is established, further inflammation induced damage of the columnar cells leads to cell mutations, notably, loss of tumor suppressor genes, TP53 and CDK2NA which in turn, increases mutation of SMAD (leads to dysregulated cell growth) and the expression of AT-rich interactive domain-containing protein 1A, ARID1A) (part of a protein complex responsible for activating genes normally silenced by chromatin structure). The final result is chromosome instability (CIN) and malignant transformation to EAC [19]. Abbreviations: AT-rich interactive domain-containing protein 1A (ARID1A), bile acid (BA), bone morphogenetic protein (BMP, growth factor), caudal homeobox gene 1 (CDX1), chromosomal instability (CIN), cyclin-dependent kinase inhibitor 2A (CDKN2A, tumor suppressor), esophageal adenocarcinoma (EAC), gastric acid esophageal reflux disease (GERD), interleukin (IL) (IL-1β, IL-6, inflammatory cytokines), squamocolumnar junction (SCJ), tumor protein 54 (TP53, tumor suppressor) (B) ESCC development.…”

Section: Introduction To Esophageal Cancermentioning

confidence: 99%

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The Distinctive Serum Metabolomes of Gastric, Esophageal and Colorectal Cancers

Ren

Rajani

Wang

2021

Cancers

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Three of the most lethal cancers in the world are the gastrointestinal cancers—gastric (GC), esophageal (EC) and colorectal cancer (CRC)—which are ranked as third, sixth and fourth in cancer deaths globally. Early detection of these cancers is difficult, and a quest is currently on to find non-invasive screening tests to detect these cancers. The reprogramming of energy metabolism is a hallmark of cancer, notably, an increased dependence on aerobic glycolysis which is often referred to as the Warburg effect. This metabolic change results in a unique metabolic profile that distinguishes cancer cells from normal cells. Serum metabolomics analyses allow one to measure the end products of both host and microbiota metabolism present at the time of sample collection. It is a non-invasive procedure requiring only blood collection which encourages greater patient compliance to have more frequent screenings for cancer. In the following review we will examine some of the most current serum metabolomics studies in order to compare their results and test a hypothesis that different tumors, notably, from EC, GC and CRC, have distinguishing serum metabolite profiles.

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“…Adult stem cells are vital for tissue/organ maintenance. Two models, the homogeneity and heterogeneity models, are proposed for self-renewal and maintenance of the proliferation-differentiation homeostasis of the mature esophageal epithelium[4, 10, 11]. The homogeneity model hypothesizes that cells in the basal layer consist of one single population that can function as the stem-like progenitors via the cell division cycle to produce daughter cells.…”

Section: Introductionmentioning

confidence: 99%

Identification and Characterization of Stem Cells in Mammalian Esophageal Stratified Squamous Epithelia

Yang

Deng

Qiao

et al. 2021

Preprint

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Somatic stem cells are essential for maintenance of cell proliferation-differentiation homeostasis in organs. Despite the importance, how the esophageal epithelium that executes its self-renewal and maintenance remains elusive. In this study, using 5-bromo-2’-deoxyuridine (BrdU) label-chase in rat and rat esophageal keratinocyte cell line-derived organoids together with genome-wide DNA methylation profiling and single-cell RNA sequencing (scRNA-seq), we identify slow cycling/quiescent stem cell population that contain high levels of hemidesmosome (HD)’s and low levels of Wnt signaling localized spatially and randomly at the basal layer of the esophageal epithelium. Pseudo-time cell trajectory from scRNA-seq indicates that cell fates begin from quiescent basal cells (the stem cells) of the basal layer that produce proliferating and/or differentiating cells in the basal layer, which, in turn, progress into differentiating cells in the suprabasal layer, ultimately transforming into differentiated keratinocytes in the differentiated layer. Perturbations of HD component expressions and/or Wnt signaling reduce stem cell in the basal layer of esophageal keratinocyte organoids, resulting in alterations of organoid formation rate, size, morphogenesis and proliferation-differentiation homeostasis. Furthermore, we show that not only high levels of HDs and low levels of Wnt signaling but also an interplay between HD and Wnt signaling defined stem cells of the basal layer in the esophageal squamous epithelium. Hence, HDs and Wnt signaling are the critical determinants for defining stem cells of the basal layer required for proliferation-differentiation homeostasis and maintenance in the mammalian esophageal squamous epithelium.

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Basal progenitor cells bridge the development, malignant cancers, and multiple diseases of esophagus

Cited by 4 publications

References 84 publications

Identification and characterization of stem cells in mammalian esophageal stratified squamous epithelia

Identification and characterization of stem cells in mammalian esophageal stratified squamous epithelia

The Distinctive Serum Metabolomes of Gastric, Esophageal and Colorectal Cancers

Identification and Characterization of Stem Cells in Mammalian Esophageal Stratified Squamous Epithelia

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