Regulation of Kit Expression in Early Mouse Embryos and ES Cells.
Amino Acid Substitution
Animals
Blastocyst
/ cytology
DNA-Binding Proteins
/ genetics
Gene Expression Regulation, Developmental
Mice
Mice, Knockout
Mouse Embryonic Stem Cells
/ cytology
Mutation, Missense
Nanog Homeobox Protein
/ genetics
Proto-Oncogene Proteins c-kit
/ biosynthesis
RNA-Binding Proteins
/ genetics
Response Elements
SOXB1 Transcription Factors
/ genetics
Transcription Factors
/ genetics
C-Kit
Embryo
Embryonic stem cells
LIF
Proliferation
Transgenic mouse
Xenogeneic stem cell transplantation
Journal
Stem cells (Dayton, Ohio)
ISSN: 1549-4918
Titre abrégé: Stem Cells
Pays: England
ID NLM: 9304532
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
24
02
2018
revised:
15
11
2018
accepted:
24
11
2018
pubmed:
20
12
2018
medline:
28
2
2020
entrez:
20
12
2018
Statut:
ppublish
Résumé
Kit is a growth factor receptor that regulates proliferation and/or survival of many embryonic and postnatal stem cell types. When mutated, it can induce malignant transformation of the host cells. To dissect the Kit role in the control of ESC pluripotency, we studied its expression during early mouse embryogenesis and during the process of ESC derivation from inner cell mass (ICM) cells. We followed the in vitro development of early mouse embryos obtained from transgenic mice carrying Kit promoter regions fused to EGFP (Kit-EGFP) and found that they initiate EGFP expression at morula stage. EGFP expression is then maintained in the blastocyst, within the ICM, and its levels increase when cultured in the presence of MAPK and GSK3β inhibitors (2i) plus LIF compared with the LIF-only condition. Kit-EGFP ESCs showed nonhomogeneous EGFP expression pattern when cultured in LIF condition, but they upregulated EGFP expression, as well as that of Sox2, Nanog, Prdm14, when shifted to 2i-LIF culture. Similarly, primordial germ cells (PGCs) in the process of embryonic germ cell (EGC) conversion showed enhanced EGFP expression in 2i-LIF. Kit expression was affected by manipulating Sox2 levels in ESCs. Chromatin immunoprecipitation experiments confirmed that Sox2 binds Kit regulatory regions containing Sox2 consensus sequences. Finally, Kit constitutive activation induced by the D814Y mutation increased ESC proliferation and cloning efficiency in vitro and in teratoma assays in vivo. Our results identify Kit as a pluripotency-responsive gene and suggest a role for Kit in the regulation of ESC proliferation. Stem Cells 2019;37:332-344.
Identifiants
pubmed: 30566254
doi: 10.1002/stem.2960
pmc: PMC8265211
mid: NIHMS1715410
doi:
Substances chimiques
DNA-Binding Proteins
0
Kit protein, mouse
0
Nanog Homeobox Protein
0
Nanog protein, mouse
0
Prdm14 protein, mouse
0
RNA-Binding Proteins
0
SOXB1 Transcription Factors
0
Sox2 protein, mouse
0
Transcription Factors
0
Proto-Oncogene Proteins c-kit
EC 2.7.10.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
332-344Subventions
Organisme : Intramural NIH HHS
ID : ZIA BC010390
Pays : United States
Informations de copyright
© AlphaMed Press 2018.
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