The development and stem cells of the esophagus

Zhang, Yongchun; Bailey, Dominique D.; Yang, Patrick; Kim, Eugene

doi:10.1242/dev.193839

Cited by 36 publications

(29 citation statements)

References 137 publications

(142 reference statements)

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“…Genetic abnormalities that affect signaling pathways responsible for normal esophageal development are described in EA and LGEA patients although there is not a single pathway responsible for the spectrum [25][26][27][28][29]. A broad gene array evaluated for expression differences between the various patient groups focused on inflammation, angiogenesis and wound healing (Fig.…”

Section: Discussionmentioning

confidence: 99%

Characterization of mesenchymal stem cells in patients with esophageal atresia

Jensen

Wanczyk

Thaker

et al. 2021

Journal of Pediatric Surgery

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Background: Preclinical studies demonstrate that tissue engineering and patient-derived stem cells can regenerate tissue. The goal of this study was to determine whether stem cells from esophageal atresia patients (EA) could be utilized for this purpose. Methods: Adipose tissue was obtained from control, esophageal atresia (EA) and long gap esophageal atresia (LGEA) patients. Mesenchymal stem cells (MSCs) were isolated, expanded, characterized and seeded onto tubular scaffolds for 6 days. Scaffolds were characterized for viability, gene expression and cytokine production. Results: The average weight of tissue from the EA and LGEA patients was 145.8mg compared to 2981 mg in controls. Despite the small amount of tissue obtained from neonatal patients, cells were expanded to cover a scaffold. After incubating 6 days on the scaffold, cells were viable and proliferating with differences in gene expression between groups. VEGFA production in the supernatant was increased in EA and LGEA patients; while IL6 production was significantly increased in the control patients. Conclusions: This study demonstrates the ability to utilize small amounts of adipose tissue from esophageal atresia patients as a cell source for regenerative medicine. Future studies will focus on use of these cells for tissue regeneration in vivo.

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Section: Discussionmentioning

confidence: 99%

Characterization of mesenchymal stem cells in patients with esophageal atresia

Jensen

Wanczyk

Thaker

et al. 2021

Journal of Pediatric Surgery

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“…Despite of extensive research, identification and determination of stem cells in the mammalian esophageal epithelia remained controversial [11]. By genetic means in mouse model system, Doupe et al, showed that the esophageal epithelium contained a single population of cells that divided stochastically to generate proliferating and differentiating daughter cells with equal possibility, thus indicating that a "reserve" slow cycling stem cell pool was not existed in the esophageal epithelium [13].…”

Section: Discussionmentioning

confidence: 99%

“…The mammalian esophagus initially originates from the anterior foregut that also gives rise to the respiratory system during embryonic development. As these organs are specified via a process of respiratoryesophageal separation (RES), the esophageal epithelium forms a simple columnar epithelium and then transforms into a stratified multi-layered epithelium [1][2][3][4]. The cellular and molecular mechanisms regulating RES and the esophageal epithelial morphogenesis during embryonic development have been extensively studied in recent years [2,[4][5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

“…As these organs are specified via a process of respiratoryesophageal separation (RES), the esophageal epithelium forms a simple columnar epithelium and then transforms into a stratified multi-layered epithelium [1][2][3][4]. The cellular and molecular mechanisms regulating RES and the esophageal epithelial morphogenesis during embryonic development have been extensively studied in recent years [2,[4][5][6][7][8][9]. However, it is less clear how the mature esophageal epithelium executes its self-renewal and maintenance of the proliferation-differentiation homeostasis.…”

Section: Introductionmentioning

confidence: 99%

“…It is made available under a preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in The copyright holder for this this version posted November 12, 2021. ; https://doi.org/10.1101/2021.11.11.468184 doi: bioRxiv preprint these cells choose randomly to remain as progenitors or differentiate into suprabasal cells [12][13][14][15]. In contrast, the heterogeneity model offers an alternative possibility where, like other organs such as colon and stomach with a simple columnar epithelium or skin with stratified squamous epithelium, the basal layer of mammalian esophagi has a slow-cycling or quiescent stem cell subpopulation that can be self-renewal, giving rise to fast-dividing progenitor cells in the basal layer and/or all other differentiated lineages in the suprabasal layers and the differentiated layers [11]. In support of this model, asymmetrical cell division and cells with specific stemness related markers were found in the basal layers of mammalian esophagi [16][17][18][19][20].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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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Primary cilia are critical for tracheoesophageal septation

Fitzsimons,

Tasouri,

Willaredt

et al. 2023

Developmental Dynamics

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IntroductionPrimary cilia play pivotal roles in the patterning and morphogenesis of a wide variety of organs during mammalian development. Here we examined murine foregut septation in the cobblestone mutant, a hypomorphic allele of the gene encoding the intraflagellar transport protein IFT88, a protein essential for normal cilia function.ResultsWe reveal a crucial role for primary cilia in foregut division, since their dramatic decrease in cilia in both the foregut endoderm and mesenchyme of mutant embryos resulted in a proximal tracheoesophageal septation defects and in the formation of distal tracheo(broncho)esophageal fistulae similar to the most common congenital tracheoesophageal malformations in humans. Interestingly, the dorsoventral patterning determining the dorsal digestive and the ventral respiratory endoderm remained intact, whereas Hedgehog signaling was aberrantly activated.ConclusionsOur results demonstrate the cobblestone mutant to represent one of the very few mouse models that display both correct endodermal dorsoventral specification but defective compartmentalization of the proximal foregut. It stands exemplary for a tracheoesophageal ciliopathy, offering the possibility to elucidate the molecular mechanisms how primary cilia orchestrate the septation process. The plethora of malformations observed in the cobblestone embryo allow for a deeper insight into a putative link between primary cilia and human VATER/VACTERL syndromes.

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The development and stem cells of the esophagus

Cited by 36 publications

References 137 publications

Characterization of mesenchymal stem cells in patients with esophageal atresia

Characterization of mesenchymal stem cells in patients with esophageal atresia

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

Primary cilia are critical for tracheoesophageal septation

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