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Reconstruction of dynamic regulatory networks reveals signaling-induced topology changes associated with germ layer specification

ABSTRACT: Reconstruction of dynamic regulatory networks reveals signaling-induced topology changes associated with germ layer specification

PROVIDER: PRJNA736973 | ENA |

REPOSITORIES: ENA

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Reconstruction of dynamic regulatory networks reveals signaling-induced topology changes associated with germ layer specification

Project description:Elucidating regulatory relationships between transcription factors (TFs) and target genes is fundamental to understanding how cells control their identity and behavior. To overcome the limited scope and scalability of experimental methods in mapping this control, computational GRN reconstruction methods have been developed to infer relationships from transcriptomic data. We developed a new computational GRN reconstruction tool called Epoch, which takes advantage of single-cell RNA sequencing to address a number of shortcomings of existing tools including low precision, low sensitivity, and the limited ability to describe network topology changes over time. We used Epoch to identify the dynamic networks and key transcriptional regulators underpinning directed differentiation of mouse embryonic stem cells, and further demonstrate that modulating signaling pathways drives topological network changes that shape cell fate potential. By integrating signaling pathways with GRN structures, we traced how Wnt activation and PI3K suppression govern mesoderm and endoderm specification, respectively.

2022-01-27 | GSE177051 | GEO

Global miRNA dosage control of embryonic germ layer specification

Project description:Global miRNA dosage control of embryonic germ layer specification

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Specification of germ layer identity in the chick gastrula.

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Functions of huntingtin in germ layer specification and organogenesis.

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Global miRNA dosage control of embryonic germ layer specification.

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Global miRNA dosage control of embryonic germ layer specification

Project description:MicroRNAs (miRNAs) have essential functions during embryonic development, and their dysregulation causes cancer. Altered global miRNA abundance is found in different tissues and tumours, which implies that precise control of miRNA dosage is important[134], but the underlying mechanism(s) of this control remain unknown. The protein complex Microprocessor, which comprises one DROSHA and two DGCR8 proteins, is essential for miRNA biogenesis. Here we identify a developmentally regulated miRNA dosage control mechanism that involves alternative transcription initiation (ATI) of DGCR8. ATI occurs downstream of a stem-loop in DGCR8 mRNA to bypass an autoregulatory feedback loop during mouse embryonic stem cell (mES cell) differentiation. Deletion of the stem-loop causes imbalanced DGCR8:DROSHA protein stoichiometry that drives irreversible Microprocessor aggregation, reduced primary miRNA processing, decreased mature miRNA abundance, and widespread de-repression of lipid metabolic mRNA targets. Although global miRNA dosage control is not essential for mES cells to exit from pluripotency, its dysregulation alters lipid metabolic pathways and interferes with embryonic development by disrupting germ layer specification in vitro and in vivo. This miRNA dosage control mechanism is conserved in humans. Our results identify a promoter switch that balances Microprocessor autoregulation and aggregation to precisely control global miRNA dosage and govern stem cell fate decisions during early embryonic development.

2021-03-24 | GSE165017 | GEO

Reconstruction of signaling networks regulating fungal morphogenesis by transcriptomics

Project description:Reconstruction of signaling networks regulating fungal morphogenesis by the expression profiling of wild-type and the temperature sensitive morphological ramosa-1 mutant. Aspergillus niger wildtype versus Ramosa mutant for 1h at 37 under controlled growth condition in 5L bioreactor

2010-05-05 | E-GEOD-17641 | biostudies-arrayexpress

Reconstruction of signaling networks regulating fungal morphogenesis by transcriptomics

Project description:Reconstruction of signaling networks regulating fungal morphogenesis by the expression profiling of wild-type and the temperature sensitive morphological ramosa-1 mutant.

2009-09-17 | GSE17641 | GEO

Muscle progenitor specification and myogenic differentiation are associated with changes in chromatin topology.

Project description:Muscle progenitor specification and myogenic differentiation are associated with changes in chromatin topology.

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Replication Timing Reveal An Epigenetic Commitment To Differentiation Prior To Germ Layer Specification (WG_CGH, RT)

Project description:Differentiation of mouse embryonic stem cells (mESCs) is accompanied by global changes in replication timing. To elucidate this reorganization process and explore its potential impact on mouse development, we constructed genome-wide replication-timing profiles of 15 independent mouse cell types representing nine different stages of early mouse development, including all three germ layers. Overall, 45% of the genome exhibits significant changes in replication timing between cell types, indicating that replication-timing regulation is more extensive than previously estimated from neural differentiation. Intriguingly, analysis of early and late epiblast cell culture models suggest that the earliest changes in development include extensive lineage-independent early-to-late replication switches that are completed at a stage equivalent to the post-implantation epiblast, prior to germ layer specification and down-regulation of key pluripotency transcription factors (Oct4/Nanog/Sox2). These changes were stable in all subsequent lineages and involved a class of irreversibly silenced genes that were re-positioned closer to the nuclear periphery. Lineage-specific, late-to-early and early-to-late replication switches followed, which created cell-type specific replication profiles. Importantly, partially reprogrammed induced pluripotent stem cells (piPSCs) failed to restore ESC-specific replication timing and transcription programs particularly within regions of lineage-independent early-to-late replication changes, as well as the inactive X-chromosome. We conclude that lineage-independent, early-to-late replication-timing switches that occur in the post-implantation epiblast embody an epigenetic commitment to differentiation prior to germ layer specification. 22 cell lines, with a total of 36 individual replicates (i.e. 14 in duplicates, 8 in single replicates)

2010-05-19 | E-GEOD-17983 | biostudies-arrayexpress

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