TY - JOUR
T1 - Origins of Metaplasia in Barrett’s Esophagus
T2 - Is this an Esophageal Stem or Progenitor Cell Disease?
AU - Zhang, Wei
AU - Wang, David H.
N1 - Publisher Copyright:
© 2018, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
PY - 2018/8/1
Y1 - 2018/8/1
N2 - The incidence of esophageal adenocarcinoma has been increasing in Western countries over the past several decades. Though Barrett’s esophagus, in which the normal esophageal squamous epithelium is replaced with metaplastic intestinalized columnar cells due to chronic damage from gastroesophageal reflux, is accepted as the requisite precursor lesion for esophageal adenocarcinoma, the Barrett’s esophagus cell of origin and the molecular mechanism underlying esophageal epithelial metaplasia remain controversial. Much effort has been dedicated towards identifying the Barrett’s esophagus cell of origin since this could lead to more effective prevention and treatment strategies for both Barrett’s esophagus and esophageal adenocarcinoma. Previously, it was hypothesized that terminally differentiated esophageal squamous cells might undergo direct conversion into specialized intestinal columnar cells via the process of transdifferentiation. However, there is increasing evidence that stem and/or progenitor cells are molecularly reprogrammed through the process of transcommitment to differentiate into the columnar cell lineages that characterize Barrett’s esophagus. Given that Barrett’s esophagus originates at the gastroesophageal junction, the boundary between the distal esophagus and gastric cardia, potential sources of these stem and/or progenitor cells include columnar cells from the squamocolumnar junction or neighboring gastric cardia, native esophageal squamous cells, native esophageal cuboidal or columnar cells from submucosal glands or ducts, or circulating bone marrow-derived cells. In this review, we focus on native esophageal specific stem and/or progenitor cells and detail molecular mediators of transcommitment based on recent insights gained from novel mouse models and clinical observations from patients.
AB - The incidence of esophageal adenocarcinoma has been increasing in Western countries over the past several decades. Though Barrett’s esophagus, in which the normal esophageal squamous epithelium is replaced with metaplastic intestinalized columnar cells due to chronic damage from gastroesophageal reflux, is accepted as the requisite precursor lesion for esophageal adenocarcinoma, the Barrett’s esophagus cell of origin and the molecular mechanism underlying esophageal epithelial metaplasia remain controversial. Much effort has been dedicated towards identifying the Barrett’s esophagus cell of origin since this could lead to more effective prevention and treatment strategies for both Barrett’s esophagus and esophageal adenocarcinoma. Previously, it was hypothesized that terminally differentiated esophageal squamous cells might undergo direct conversion into specialized intestinal columnar cells via the process of transdifferentiation. However, there is increasing evidence that stem and/or progenitor cells are molecularly reprogrammed through the process of transcommitment to differentiate into the columnar cell lineages that characterize Barrett’s esophagus. Given that Barrett’s esophagus originates at the gastroesophageal junction, the boundary between the distal esophagus and gastric cardia, potential sources of these stem and/or progenitor cells include columnar cells from the squamocolumnar junction or neighboring gastric cardia, native esophageal squamous cells, native esophageal cuboidal or columnar cells from submucosal glands or ducts, or circulating bone marrow-derived cells. In this review, we focus on native esophageal specific stem and/or progenitor cells and detail molecular mediators of transcommitment based on recent insights gained from novel mouse models and clinical observations from patients.
KW - Barrett’s esophagus
KW - Squamous progenitor cell
KW - Squamous stem cell
KW - Transcommitment
KW - Transdifferentiation
UR - http://www.scopus.com/inward/record.url?scp=85045762729&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85045762729&partnerID=8YFLogxK
U2 - 10.1007/s10620-018-5069-5
DO - 10.1007/s10620-018-5069-5
M3 - Review article
C2 - 29675663
AN - SCOPUS:85045762729
SN - 0163-2116
VL - 63
SP - 2005
EP - 2012
JO - Digestive Diseases and Sciences
JF - Digestive Diseases and Sciences
IS - 8
ER -