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LncRNA Mrhl orchestrates differentiation programs in mouse embryonic stem cells through chromatin mediated regulation

ABSTRACT: LncRNA Mrhl orchestrates differentiation programs in mouse embryonic stem cells through chromatin mediated regulation

PROVIDER: PRJNA670429 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12858434_1.fastq.gz	Fastqsanger.gz
	SRR12858434_2.fastq.gz	Fastqsanger.gz
	SRR12858435_1.fastq.gz	Fastqsanger.gz
	SRR12858435_2.fastq.gz	Fastqsanger.gz
	SRR12858436_1.fastq.gz	Fastqsanger.gz

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LncRNA Mrhl orchestrates differentiation programs in mouse embryonic stem cells through chromatin mediated regulation

Project description:Earlier studies from our lab have characterized lncRNA Mrhl extensively in the context of male germ cell meiotic commitment and spermatogenesis, unraveling a negative feedback loop between Mrhl and a highly conserved context-dependant developmental pathway such as the WNT pathway. LncRNAs have been implicated for their functional roles in diverse developmental phenomena, cell fate specification events and differentiation of stem cells into various lineages. In purview of these, we aimed towards exploring lncRNA Mrhl and its functional relevance in mouse embryonic stem cells (mESCs) to understand its role in development and differentiation. Towards this end, we have addressed the targets of Mrhl in mouse embryonic stem cells. Our studies have revealed developmental processes, lineage specific transcription factors and lineage specific cell adhesion and receptor pathway genes to be majorly dysregulated upon Mrhl knockdown in mESCs with no perturbation in pluripotency status of the cells. This study has revealed context-dependant regulation of target genes by lncRNA Mrhl and implicated its role in regulating differentiation events in mESCs.

2020-10-23 | GSE159757 | GEO

Enhancer architecture-dependent multilayered transcriptional regulation orchestrates RA signal-induced early differentiation of ESC

Project description:Signaling pathway driven target gene transcriptions are critical for fate determination of embryonic stem cells (ESC), but enhancer architecture-dependent transcriptional regulation remains largely unclear in this process. Here, we described a complex enhancer architecture-dependent multilayered transcriptional regulation that orchestrates retinoic acid (RA) signal-induced early differentiation of ESC. Specifically, we identified Hoxa1 and lncRNA Halr1 as the direct downstream target genes of RA signal. Chromosome conformation capture based screens show that increased enhancer interactions promoted by RA signal are essential for Hoxa1 and Halr1 expressions during early ESC differentiation. Furthermore, we find that HOXA1 promotes Halr1 expression through direct binding to enhancers; conversely, absence of Halr1 RNA enhances interaction between Hoxa1 chromatin and multiple enhancers, but weakens interaction with HoxA cluster internal chromatin, thereby promoting RA signal-induced Hoxa1 overactivation and early differentiation of ESC. These results indicate that Halr1 binds to chromatin not only acts as a brake to orchestrate interaction between enhancers and Hoxa1 chromatin, but also acts as a binder to maintain chromatin interaction within HoxA cluster. In summary, these findings reveal a complex multilayered transcriptional regulation involving the synergistic regulation of enhancer, transcription factor and lncRNA, and that increases our understanding of the intrinsic molecular mechanisms of RA signal-induced ESC differentiation.

2021-04-16 | GSE169058 | GEO

The lncRNA Hand2os1/Uph locus orchestrates heart development through regulation of precise expression HAND2

Project description:Exploration and dissection of potential actions and effects of long noncoding RNA (lncRNA) in animals remain challenging. Here using multiple knockout mouse models and single-cell RNA sequencing, we demonstrate that the divergent lncRNA Hand2os1/Uph has a key, complex modulatory effect on the expression of its neighboring gene HAND2 and subsequently on heart development and function. Short deletion of the Hand2os1 promoter in mouse diminishes Hand2os1 transcription to 8~32%, but fails to affect HAND2 expression and yields no discernable heart phenotypes. Interestingly, full-length deletion of Hand2os1 in mouse causes moderate yet prevalent upregulation of HAND2 in hundreds of cardiac cells, leading to profound biological consequences, including dysregulated cardiac gene programs, congenital heart defects and perinatal lethality. We propose that the Hand2os1 locus dampens HAND2 expression to restrain cardiomyocyte proliferation, thereby orchestrating a balanced development of cardiac cell lineages. This study highlights the regulatory complexity of the lncRNA Hand2os1 on HAND2 expression, emphasizing the need for complementary genetic and single-cell approaches to delineate the function and primary molecular effects of an lncRNA in animals.

2019-06-14 | GSE102935 | GEO

Divergent transcription of lncRNA/mRNA gene pairs in embryonic stem cells

Project description:Many long non-coding RNA (lncRNA) species have been identified in mammalian cells, but the genomic origin, regulation and function of these molecules in individual cell types is poorly understood. We have generated comprehensive catalogs of lncRNA species expressed in human and murine embryonic stem cells (ESCs) and mapped their genomic origin. A surprisingly large fraction of these transcripts (>60%) originate from divergent transcription at promoters of active protein-coding genes. The divergently transcribed lncRNA/mRNA gene pairs exhibit coordinated changes in transcription when ESCs are differentiated into endoderm. A significant number of the divergently transcribed lncRNAs/mRNA pairs are conserved between human and mouse ESCs. Disruption of promoter-associated lncRNA orthologs in a zebrafish model of early development causes gross developmental defects. Our results reveal that transcription of most lncRNA genes is coordinated with transcription of protein-coding genes and that these lncRNAs have roles in early development. Analysis of genome-wide lncRNA transcription in human embryonic stem cells and early differentiation using RNA-seq, GRO-seq and ChIP-seq

2013-01-02 | E-GEOD-41009 | biostudies-arrayexpress

Hnrnpk orchestrates embryonic growth plate development via regulating glycolysis

Project description:Hnrnpk orchestrates embryonic growth plate development via regulating glycolysis

| PRJNA809664 | ENA

Unifying Developmental Programs for Embryonic and Post-Embryonic Neurogenesis in the Zebrafish Retina

Project description:It provides an opportunity to make the first comparative study of molecular programs used by embryonic and post-embryonic neurogenic programs in the vertebrate retina.

2020-05-19 | GSE122680 | GEO

Unifying Developmental Programs for Embryonic and Post-Embryonic Neurogenesis in the Zebrafish Retina

Project description:Unifying Developmental Programs for Embryonic and Post-Embryonic Neurogenesis in the Zebrafish Retina

| PRJNA506002 | ENA

Opposing roles for the lncRNA Haunt and its genomic locus in regulating HOXA gene activation during embryonic stem cell differentiation

Project description:Long noncoding RNAs (lncRNAs) have been implicated in controlling various aspects of embryonic stem cell (ESC) biology, although the functions of specific lncRNAs, and the molecular mechanisms through which they act, remain unclear. Here, we demonstrate discrete and opposing roles for the lncRNA transcript Haunt and its genomic locus in regulating the HOXA gene cluster during ESC differentiation. Reducing or enhancing Haunt expression, with minimal disruption of the Haunt locus, led to up- or down-regulation of HOXA genes, respectively. In contrast, increasingly large genomic deletions within the Haunt locus attenuated HOXA activation. The Haunt DNA locus contains potential enhancers of HOXA activation, whereas Haunt RNA acts to prevent aberrant HOXA expression. This work reveals a multi-faceted model of lncRNA-mediated transcriptional regulation of the HOXA cluster, with distinct roles for a lncRNA transcript and its genomic locus, while illustrating the power of rapid CRISPR/Cas9-based genome editing for assigning lncRNA functions. All RNA-seq(s) were designed to reveal the differentially expressed genes among different stages of ESCs differentiation, or differentially expressed genes between wild-type or Haunt or HOXA mutant cells during RA-induced differentiation. All ChIRP-Seq were used to reveal the DNA or RNA targets of Haunt before or after RA treatment.

2015-04-20 | E-GEOD-58514 | biostudies-arrayexpress

Spatiotemporal role of the lncRNA Evx1as in embryonic patterning

Project description:Spatiotemporal role of the lncRNA Evx1as in embryonic patterning

| PRJNA412253 | ENA

Chromatin Structure and Gene Expression Programs of Human Embryonic and Induced Pluripotent Stem Cells

Project description:This SuperSeries is composed of the following subset Series: GSE23402: Chromatin Structure and Gene Expression Programs of Human Embryonic and Induced Pluripotent Stem Cells (Affymetrix) GSE23455: Chromatin Structure and Gene Expression Programs of Human Embryonic and Induced Pluripotent Stem Cells (ChIP-seq) Refer to individual Series

2010-08-08 | E-GEOD-22499 | biostudies-arrayexpress

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