Cited by 238Pluripotent Stem Cells ResearchDevelopmental Biology and Gene RegulationReproductive Biology and Fertility
GATA6 Levels Modulate Primitive Endoderm Cell Fate Choice and Timing in the Mouse Blastocyst
Open accessSchrode, Nadine, Saiz, Néstor, Di Talia, Stefano, Hadjantonakis, Anna-Katerina·2014·Developmental Cell
Abstract
Cells of the inner cell mass (ICM) of the mouse blastocyst differentiate into the pluripotent epiblast or the primitive endoderm (PrE), marked by the transcription factors NANOG and GATA6, respectively. To investigate the mechanistic regulation of this process, we applied an unbiased, quantitative, single-cell-resolution image analysis pipeline to analyze embryos lacking or exhibiting reduced levels of GATA6. We find that Gata6 mutants exhibit a complete absence of PrE and demonstrate that GATA6 levels regulate the timing and speed of lineage commitment within the ICM. Furthermore, we show that GATA6 is necessary for PrE specification by FGF signaling and propose a model where interactions between NANOG, GATA6, and the FGF/ERK pathway determine ICM cell fate. This study provides a framework for quantitative analyses of mammalian embryos and establishes GATA6 as a nodal point in the gene regulatory network driving ICM lineage specification.
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Crossref · 10.1016/j.devcel.2014.04.011
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ICM cell fate specification is driven in part by lineage-specific TFs Gata6 and Nanog, co-expressed in uncommitted ICM and exclusively expressed in and required for PrE and EPI respectively.
“ICM cell fate specification is driven in part by the lineage-specific transcription factors (TFs) Gata6 and Nanog, which are co-expressed in uncommitted ICM, and exclusively expressed in, and required for, PrE and EPI respectively23,24.”
From The emergent landscape of the mouse gut endoderm at single-cell resolution (2019) · cites this paper as [24]
The Introduction and Results describe GATA6 and NANOG as lineage-specific transcription factors that are initially co-expressed in ICM cells and later become mutually exclusive in PrE and EPI precursors. The Results establish that GATA6 is required for PrE specification. Our copy identifies NANOG with EPI but does not establish that NANOG is required for EPI specification. (LLM, conf=0.88)
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- Authors
- Schrode, N., Saiz, N., Di Talia, S., & Hadjantonakis, A.-K.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Hadjantonakis, Anna-Katerina
- Venue
- Developmental Cell
- Publisher
- Elsevier BV
- Published
- 2014-05
- Volume
- 29
- Issue
- 4
- Pages
- 454-467
- ISSN
- 1534-5807 (ISSN-L)
- PMC
- PMC4103658
- OpenAlex
- W2024759663
- Cited by
- 238
- References
- 49
- Citations by year
- 2026: 13 · 2025: 23 · 2024: 11 · 2023: 25 · 2022: 25 · 2021: 21 · 2020: 21 · 2019: 12 · 2018: 27 · 2017: 21 · 2016: 16 · 2015: 18 · 2014: 5
- FWCI
- 8.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Developmental Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (1k99hd074670-01)
- National Cancer Institute (P30CA008748)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK084391)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD052115, R00HD074670, K99-HD074670)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Keywords
- GATA6, primitive endoderm, inner cell mass, blastocyst, Nanog, FGF signaling, ERK signaling, lineage commitment, epiblast, gene regulatory networks, single-cell image analysis, mouse embryo
- MeSH terms
- Nanog Homeobox Protein, Animals, Benzamides, Cell Differentiation, Diphenylamine, Embryo, Mammalian, Endoderm, Mice, Knockout, Homeodomain Proteins, Gene Expression Regulation, Developmental, Cell Lineage, MAP Kinase Signaling System, HMGB Proteins, Embryo Culture Techniques, Extracellular Signal-Regulated MAP Kinases, GATA6 Transcription Factor, Mice, Fibroblast Growth Factor 4, Blastocyst Inner Cell Mass, SOXF Transcription Factors
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