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Regulation of neuronal commitment in mouse embryonic stem cells by the Reno1/Bahcc1 locus.

ABSTRACT: Mammalian genomes encode thousands of long noncoding RNAs (lncRNAs), yet the biological functions of most of them remain unknown. A particularly rich repertoire of lncRNAs found in mammalian brain and in the early embryo. We used RNA-seq and computational analysis to prioritize lncRNAs that may regulate commitment of pluripotent cells to a neuronal fate and perturbed their expression prior to neuronal differentiation. Knockdown by RNAi of two highly conserved and well-expressed lncRNAs, Reno1 (2810410L24Rik) and lnc-Nr2f1, decreased the expression of neuronal markers and led to massive changes in gene expression in the differentiated cells. We further show that the Reno1 locus forms increasing spatial contacts during neurogenesis with its adjacent protein-coding gene Bahcc1. Loss of either Reno1 or Bahcc1 leads to an early arrest in neuronal commitment, failure to induce a neuronal gene expression program, and to global reduction in chromatin accessibility at regions that are marked by the H3K4me3 chromatin mark at the onset of differentiation. Reno1 and Bahcc1 thus form a previously uncharacterized circuit required for the early steps of neuronal commitment.

SUBMITTER: Hezroni H

PROVIDER: S-EPMC7645239 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Regulation of neuronal commitment in mouse embryonic stem cells by the Reno/Bahcc1 locus

Project description:Regulation of neuronal commitment in mouse embryonic stem cells by the Reno/Bahcc1 locus

2020-09-13 | GSE124517 | GEO

Regulation of neuronal commitment in mouse embryonic stem cells by the Reno/Bahcc1 locus

Project description:Regulation of neuronal commitment in mouse embryonic stem cells by the Reno/Bahcc1 locus

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Transcriptome analysis reveals determinant stages controlling human embryonic stem cell commitment to neuronal cells.

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STRAP regulates alternative splicing fidelity during lineage commitment of mouse embryonic stem cells.

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The role of Importin-?s in the maintenance and lineage commitment of mouse embryonic stem cells.

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| S-EPMC3907685 | biostudies-literature

MicroRNA-124a inhibits endoderm lineage commitment by targeting Sox17 and Gata6 in mouse embryonic stem cells.

Project description:The role of microRNAs (miRNAs) during mouse early development, especially in endoderm germ layer formation, is largely unknown. Here, via miRNA profiling during endoderm differentiation, we discovered that miR-124a negatively regulates endoderm lineage commitment in mouse embryonic stem cells (mESCs). To further investigate the functional role of miR-124a in early stages of differentiation, transfection of embryoid bodies with miR-124a mimic was performed. We showed that overexpression of miR-124a inhibits endoderm differentiation in vitro through targeting the 3'-untranslated region (UTR) of Sox17 and Gata6, revealing the existence of interplay between miR-124a and the Sox17/Gata6 transcription factors in hepato-specific gene regulation. In addition, we presented a feasible in vivo system that utilizes teratoma and gene expression profiling from microarray to quantitatively evaluate the functional role of miRNA in lineage specification. We demonstrated that ectopic expression of miR-124a in teratomas by intratumor delivery of miR-124a mimic and Atelocollagen, significantly suppressed endoderm and mesoderm lineage differentiation while augmenting the differentiation into ectoderm lineage. Collectively, our findings suggest that miR-124a plays a significant role in mESCs lineage commitment.

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