iPSCs derived from esophageal atresia patients reveal SOX2 dysregulation at the anterior foregut stage.
Anterior foregut
Esophageal atresia/tracheoesophageal fistula
Esophageal organoids
iPSCs
Journal
Disease models & mechanisms
ISSN: 1754-8411
Titre abrégé: Dis Model Mech
Pays: England
ID NLM: 101483332
Informations de publication
Date de publication:
01 11 2022
01 11 2022
Historique:
received:
03
03
2022
accepted:
18
10
2022
pubmed:
2
11
2022
medline:
30
11
2022
entrez:
1
11
2022
Statut:
ppublish
Résumé
A series of well-regulated cellular and molecular events result in the compartmentalization of the anterior foregut into the esophagus and trachea. Disruption of the compartmentalization process leads to esophageal atresia/tracheoesophageal fistula (EA/TEF). The cause of EA/TEF remains largely unknown. Therefore, to mimic the early development of the esophagus and trachea, we differentiated induced pluripotent stem cells (iPSCs) from EA/TEF patients, and iPSCs and embryonic stem cells from healthy individuals into mature three-dimensional esophageal organoids. CXCR4, SOX17 and GATA4 expression was similar in both patient-derived and healthy endodermal cells. The expression of the key transcription factor SOX2 was significantly lower in the patient-derived anterior foregut. We also observed an abnormal expression of NKX2.1 (or NKX2-1) in the patient-derived mature esophageal organoids. At the anterior foregut stage, RNA sequencing revealed the critical genes GSTM1 and RAB37 to be significantly lower in the patient-derived anterior foregut. We therefore hypothesize that a transient dysregulation of SOX2 and the abnormal expression of NKX2.1 in patient-derived cells could be responsible for the abnormal foregut compartmentalization.
Identifiants
pubmed: 36317486
pii: 283171
doi: 10.1242/dmm.049541
pmc: PMC10655818
pii:
doi:
Substances chimiques
SOX2 protein, human
0
SOXB1 Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : CIHR
ID : PJT-156408
Pays : Canada
Organisme : CIHR
ID : PJT-174993
Pays : Canada
Informations de copyright
© 2022. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interests The authors declare no competing or financial interests.
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