Induction of pluripotency in human somatic cells via a primitive streak-like state
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PROVIDER: PRJNA217187 | ENA |
REPOSITORIES: ENA
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Project description:During mammalian embryonic development, the primitive streak is initiates the differentiation of pluripotent epiblast cells into germ layers. Pluripotency can be reacquired in committed somatic cells using a combination of handful transcription factors, such as OCT3/4, SOX2, KLF4 and c-MYC (hereafter referred to as OSKM), albeit with low efficiency . Here we show that, during the OSKM-induced reprogramming process toward pluripotency in human cells, intermediate cells transiently show gene expression profiles resembling mesendoderm, which is a major component of the primitive streak. Based on these findings, we discover that forkhead box H1 (FOXH1), a transcription factor required for anterior primitive streak specification during early development, significantly enhances the reprogramming efficiency of human fibroblasts by promoting their maturation, including the mesenchymal to epithelial transition and the activation of late pluripotent markers. These results demonstrate that during the reprogramming process, human somatic cells go through a transient state that resembles mesendoderm.
2014-04-24 | GSE50206 | GEO
Project description:During mammalian embryonic development, the primitive streak is initiates the differentiation of pluripotent epiblast cells into germ layers. Pluripotency can be reacquired in committed somatic cells using a combination of handful transcription factors, such as OCT3/4, SOX2, KLF4 and c-MYC (hereafter referred to as OSKM), albeit with low efficiency . Here we show that, during the OSKM-induced reprogramming process toward pluripotency in human cells, intermediate cells transiently show gene expression profiles resembling mesendoderm, which is a major component of the primitive streak. Based on these findings, we discover that forkhead box H1 (FOXH1), a transcription factor required for anterior primitive streak specification during early development, significantly enhances the reprogramming efficiency of human fibroblasts by promoting their maturation, including the mesenchymal to epithelial transition and the activation of late pluripotent markers. These results demonstrate that during the reprogramming process, human somatic cells go through a transient state that resembles mesendoderm. Human differentiated progeny derived from pluripotent stem cells, N=13 Human undifferentiated pluripotent stem cells, N=6 Transgenic ESC line, N=6 Human tissues, N=29 Human tissue-derived cells, N=20 Human nascent reprogrammed cells, N=95 Mouse cells, N=12
2014-04-24 | E-GEOD-50206 | biostudies-arrayexpress
Project description:In birds and mammals, all mesoderm cells are generated from the primitive streak. Nascent mesoderm cells contain unique dorso-ventral (D/V) identities depending on their relative ingression position along the streak. Molecular mechanisms controlling this initial phase of mesoderm diversification are not well-understood. Using chick model, we generated high-quality transcriptomic datasets of different streak regions and analyzed their molecular heterogeneity.
2010-07-29 | GSE22230 | GEO
Project description:Characterization of the signaling requirements to determine primitive streak and neuroectoderm fates in mouse embryonic stem cells.
2022-01-20 | E-MTAB-10242 | biostudies-arrayexpress
Project description:In birds and mammals, all mesoderm cells are generated from the primitive streak. Nascent mesoderm cells contain unique dorso-ventral (D/V) identities depending on their relative ingression position along the streak. Molecular mechanisms controlling this initial phase of mesoderm diversification are not well-understood. Using chick model, we generated high-quality transcriptomic datasets of different streak regions and analyzed their molecular heterogeneity. Streak tissues were dissected from stage-matched HH4 chick embryos and were further divided into four equal pieces along its anterio-posterior length (termed “A”, “B”, “C” and “D”, with “A” representing most anterior and therefore most dorsal and “D” most posterior and therefore most ventral). Each of the four regions was represented by three independent samples (n=3), with each sample containing 5-7 μg total RNA derived from 85-93 pooled pieces. 5 μg of RNA from each sample were used to screen Affymetrix Chicken Genome Array without an amplification step.
2010-07-29 | E-GEOD-22230 | biostudies-arrayexpress
Project description:scRNA-Seq analysis of differentiation to primitive streak fate of mouse embryonic stem cells
2022-01-20 | E-MTAB-10243 | biostudies-arrayexpress
Project description:Molecular characterisation of the primitive streak cells and cardiac progenitors
2021-03-16 | GSE153789 | GEO
Project description:The mechanism governing the transition of human embryonic stem cells towards differentiated cells is only partially understood. To explore this transition, the activity and expression of the ubiquitous phosphoinositide-3-kinase (PI3K α and β) were modulated. This study reports a pathway that dismantles the repression imposed by the EZH2 polycomb repressor on an essential stemness gene, NODAL, and on transcription factors required at differentiation to trigger primitive streak formation. The primitive streak is the site where gastrulation begins to give rise to the three embryonic cell layers from which all human tissues derive. The pathway involves an essential PI3Kβ-non-catalytic action for control of active-RAC1 levels, c-Jun-Nterminal-kinase activation and nuclear β-CATENIN accumulation. β-CATENIN deposition at promoters triggers the release of EZH2 repressor permitting both stemness maintenance (through control of NODAL) and correct differentiation, by allowing primitive streak master genes expression. PI3Kβ -mediated epigenetic control of EZH2/β-CATENIN might be modulated to direct stem cell differentiation.
2022-07-27 | GSE202163 | GEO
Project description:EpiSCs established from murine epiblast were differentiated to posterior primitive streak (PPS) and analyzed using scRNA-seq to investigate identity and homogeneity of the resulting population.
2022-11-30 | E-MTAB-12106 | biostudies-arrayexpress
Project description:Canonical Wnt and Nodal signaling are both required for induction of the primitive streak (PS), which guides organization of the early embryo. The Wnt effector β-catenin is thought to function in these early lineage specification decisions via transcriptional activation of Nodal signaling. Here, we demonstrate a broader role for β-catenin in PS formation by analyzing its genome-wide binding in a human embryonic stem cell model of PS induction. β-catenin occupies regulatory regions in numerous PS and neural crest genes, and direct interactions between β-catenin and the Nodal effectors SMAD2/3 are required at these regions for PS gene activation. Furthermore, OCT4 binding in proximity to these sites is likewise required for PS induction, suggesting a collaborative interaction between β-catenin and OCT4. Induction of neural crest genes by β-catenin is repressed by SMAD2/3, ensuring proper lineage specification. This study provides mechanistic insight into how Wnt signaling controls early cell lineage decisions.
2015-03-31 | GSE58476 | GEO