Loss of TBX3 enhances pancreatic progenitor generation from human pluripotent stem cells.
Animals
Blotting, Western
Cell Differentiation
/ genetics
Cell Line
Gene Expression Profiling
/ methods
Hepatocytes
/ cytology
Humans
Induced Pluripotent Stem Cells
/ metabolism
Mice
Mutation
Pancreas
/ cytology
Pluripotent Stem Cells
/ metabolism
RNA-Seq
/ methods
Reverse Transcriptase Polymerase Chain Reaction
Species Specificity
T-Box Domain Proteins
/ genetics
TBX3
development
liver
pancreas
Journal
Stem cell reports
ISSN: 2213-6711
Titre abrégé: Stem Cell Reports
Pays: United States
ID NLM: 101611300
Informations de publication
Date de publication:
09 11 2021
09 11 2021
Historique:
received:
12
10
2020
revised:
13
09
2021
accepted:
14
09
2021
pubmed:
16
10
2021
medline:
15
3
2022
entrez:
15
10
2021
Statut:
ppublish
Résumé
Tbx3 has been identified as a regulator of liver development in the mouse, but its function in human liver development remains unknown. TBX3 mutant human pluripotent stem cell (PSC) lines were generated using CRISPR/Cas9 genome editing. TBX3 loss led to impaired liver differentiation and an upregulation of pancreatic gene expression, including PDX1, during a hepatocyte differentiation protocol. Other pancreatic genes, including NEUROG3 and NKX2.2, displayed more open chromatin in the TBX3 mutant hepatoblasts. Using a pancreatic differentiation protocol, cells lacking TBX3 generated more pancreatic progenitors and had an enhanced pancreatic gene expression signature at the expense of hepatic gene expression. These data highlight a potential role of TBX3 in regulating hepatic and pancreatic domains during foregut patterning, with implications for enhancing the generation of pancreatic progenitors from PSCs.
Identifiants
pubmed: 34653400
pii: S2213-6711(21)00480-X
doi: 10.1016/j.stemcr.2021.09.004
pmc: PMC8580886
pii:
doi:
Substances chimiques
T-Box Domain Proteins
0
TBX3 protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2617-2627Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK118155
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK123162
Pays : United States
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
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