iPSCs derived from esophageal atresia patients reveal SOX2 dysregulation at the anterior foregut stage.
Dis Model Mech
; 15(11)2022 11 01.
Article
em En
| MEDLINE
| ID: mdl-36317486
ABSTRACT
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.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fístula Traqueoesofágica
/
Atresia Esofágica
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Células-Tronco Pluripotentes Induzidas
Tipo de estudo:
Etiology_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article