STAT3 modulates reprogramming efficiency of human somatic cells; insights from autosomal dominant Hyper IgE syndrome caused by STAT3 mutations.
Adolescent
Adult
Aged
Alleles
Amino Acid Substitution
Cells, Cultured
Child
Disease Susceptibility
Fibroblasts
/ metabolism
Genetic Predisposition to Disease
Genotype
Humans
Immunoglobulin E
/ blood
Induced Pluripotent Stem Cells
/ cytology
Job Syndrome
/ etiology
Loss of Function Mutation
Middle Aged
Mutation
STAT3 Transcription Factor
/ genetics
Young Adult
Hyper IgE syndrome
Reprogramming
STAT3
iPSC
Journal
Biology open
ISSN: 2046-6390
Titre abrégé: Biol Open
Pays: England
ID NLM: 101578018
Informations de publication
Date de publication:
10 09 2020
10 09 2020
Historique:
pubmed:
26
6
2020
medline:
2
10
2021
entrez:
26
6
2020
Statut:
epublish
Résumé
Human induced pluripotent stem cell (iPSC) technology has opened exciting opportunities for stem-cell-based therapy. However, its wide adoption is precluded by several challenges including low reprogramming efficiency and potential for malignant transformation. Better understanding of the molecular mechanisms of the changes that cells undergo during reprograming is needed to improve iPSCs generation efficiency and to increase confidence for their clinical use safety. Here, we find that dominant negative mutations in STAT3 in patients with autosomal-dominant hyper IgE (Job's) syndrome (AD-HIES) result in greatly reduced reprograming efficiency of primary skin fibroblasts derived from skin biopsies. Analysis of normal skin fibroblasts revealed upregulation and phosphorylation of endogenous signal transducer and activator of transcription 3 (STAT3) and its binding to the
Identifiants
pubmed: 32580970
pii: bio.052662
doi: 10.1242/bio.052662
pmc: PMC7502598
pii:
doi:
Substances chimiques
STAT3 Transcription Factor
0
STAT3 protein, human
0
Immunoglobulin E
37341-29-0
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2020. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interestsThe authors declare no competing or financial interests.
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