KLF family members KLF4 and KLF7 regulate corneal epithelium
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PROVIDER: PRJNA369788 | ENA |
REPOSITORIES: ENA
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Project description:While the regulatory landscape during stem cell differentiation has been well characterized, the shared and unique regulatory mechanisms in different ectodermally-derived epithelial cells have not been well described. Through defining the complement of super enhancers and typical enhancers in corneal epithelium for the first time, we show that regulatory regions are often shared between cell types of the same lineage, and that corneal super enhancers are already marked as potential regulatory domains in embryonic stem cells. Through the enrichment of KLF motifs in enhancers, we identified and defined a novel role for Kruppel family member KLF7 in promoting the corneal progenitor cell state, in many cases working antagonistically to corneal differentiation promoting KLF4. Our work highlights the importance of balance between proliferation and differentiation, both for proper tissue development and for homeostasis.
2017-06-01 | GSE94469 | GEO
Project description:While the regulatory landscape during stem cell differentiation has been well characterized, the shared and unique regulatory mechanisms in different ectodermally-derived epithelial cells have not been well described. Through defining the complement of super enhancers and typical enhancers in corneal epithelium for the first time, we show that regulatory regions are often shared between cell types of the same lineage, and that corneal super enhancers are already marked as potential regulatory domains in embryonic stem cells. Through the enrichment of KLF motifs in enhancers, we identified and defined a novel role for Kruppel family member KLF7 in promoting the corneal progenitor cell state, in many cases working antagonistically to corneal differentiation promoting KLF4. Our work highlights the importance of balance between proliferation and differentiation, both for proper tissue development and for homeostasis.
2017-06-01 | GSE94468 | GEO
Project description:While the regulatory landscape during stem cell differentiation has been well characterized, the shared and unique regulatory mechanisms in different ectodermally-derived epithelial cells have not been well described. Through defining the complement of super enhancers and typical enhancers in corneal epithelium for the first time, we show that regulatory regions are often shared between cell types of the same lineage, and that corneal super enhancers are already marked as potential regulatory domains in embryonic stem cells. Through the enrichment of KLF motifs in enhancers, we identified and defined a novel role for Kruppel family member KLF7 in promoting the corneal progenitor cell state, in many cases working antagonistically to corneal differentiation promoting KLF4. Our work highlights the importance of balance between proliferation and differentiation, both for proper tissue development and for homeostasis.
2017-06-01 | GSE94470 | GEO
Project description:KLF family members KLF4 and KLF7 regulate corneal epithelium [siKLF4_undifferentiated]
| PRJNA369792 | ENA
Project description:KLF family members KLF4 and KLF7 regulate corneal epithelium [siKLF7_undifferentiated]
| PRJNA369796 | ENA
Project description:KLF family members KLF4 and KLF7 regulate corneal epithelium [siKLF4-siKLF7_differentiation]
| PRJNA369795 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2017-06-01 | GSE94472 | GEO
Project description:This experiment is part of the FunGenES project (FunGenES - Functional Genomics in Embryonic Stem Cells partially funded by the 6th Framework Programme of the European Union, http://www.fungenes.org). The experiment was conducted at Inserm U846, Bron, France. Aim: Kru_ppel-like factors (Klf) 4 and 5 are two closely related members of the Klf family, known to play key roles in somatic cell reprogramming and in self-renewal of pluripotent stem cells. In this study, we focused on the functional divergence between Klf4 and Klf5. We showed that Klf4 and Klf5 regulate the expression of distinct subsets of genes. Klf4 negatively regulates the expression of endodermal markers, some of which encode transcription factors involved in the commitment of pluripotent system cells to endoderm differentiation. In contrast, Klf5 negatively regulates the expression of mesodermal markers, some of which controls commitment to the mesoderm lineage. Functional studies with reporter cell lines indicate that knockdown of Klf4 enhances differentiation toward visceral endoderm, mesendoderm, and definitive endoderm, whereas knockdown of Klf5 specifically enhances differentiation toward mesoderm. Thus, additive functions of Klf4 and Klf5 secure pluripotent stem cell propagation by inhibiting endoderm and mesoderm differentiation.
2014-04-28 | E-MTAB-1838 | biostudies-arrayexpress
Project description:This experiment is a follow-up experiment of the FunGenES project (FunGenES - Functional Genomics in Embryonic Stem Cells partially funded by the 6th Framework Programme of the European Union, http://www.fungenes.org). The experiment was conducted at Inserm U846, Bron, France. Aim: Kru_ppel-like factors (Klf) 4 and 5 are two closely related members of the Klf family, known to play key roles in somatic cell reprogramming and in self-renewal of pluripotent stem cells. In this study, we focused on the functional divergence between Klf4 and Klf5. We showed that Klf4 and Klf5 regulate the expression of distinct subsets of genes. Klf4 negatively regulates the expression of endodermal markers, some of which encode transcription factors involved in the commitment of pluripotent system cells to endoderm differentiation. In contrast, Klf5 negatively regulates the expression of mesodermal markers, some of which controls commitment to the mesoderm lineage. Functional studies with reporter cell lines indicate that knockdown of Klf4 enhances differentiation toward visceral endoderm, mesendoderm, and definitive endoderm, whereas knockdown of Klf5 specifically enhances differentiation toward mesoderm. Thus, additive functions of Klf4 and Klf5 secure pluripotent stem cell propagation by inhibiting endoderm and mesoderm differentiation.
2014-04-28 | E-MTAB-1839 | biostudies-arrayexpress
Project description:In skeletal muscle differentiation, muscle-specific genes are regulated by two groups of transcription factors, the MyoD and MEF2 families, which work together to drive the differentiation process. Here we show that ERK5 regulates muscle cell fusion through Klf transcription factors. The inhibition of ERK5 activity suppresses muscle cell fusion with minimal effects on the expression of MyoD, MEF2, and their target genes. Promoter analysis coupled to microarray assay reveals that Klf-binding motifs are highly enriched in the promoter regions of ERK5-dependent upregulated genes. Remarkably, Klf2 and Klf4 expression are also upregulated during differentiation in an ERK5-dependent manner, and knockdown of Klf2 or Klf4 specifically suppresses muscle cell fusion. Moreover, we show that the Sp1 transcription factor links ERK5 to Klf2/4, and that nephronectin, a Klf transcriptional target, is involved in muscle cell fusion. Therefore, an ERK5/Sp1/Klf module plays a key role in the fusion process during skeletal muscle differentiation.
2011-02-21 | GSE25827 | GEO