A multifunctional locus controls motor neuron differentiation through short and long non coding RNAs
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ABSTRACT:
PROVIDER: PRJNA731036 | ENA |
REPOSITORIES: ENA
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Project description:The transition from dividing progenitors into post-mitotic motor neurons is orchestrated by a series of events mainly studied at the transcriptional level by analyzing the activity of specific programming transcription factors. In this work, we describe that a motor neuron-specific transcriptional unit, harboring a lncRNA (lncMN2-203) and two miRNAs (miR-325-3p and miR-384-5p), controls such transition at the post-transcriptional level. Through the use of in vitro differentiation of mESC and single-cell sequencing of CRISPR/Cas9 mutants, we demonstrate that lncMN2-203 affects motor neuron differentiation by sponging miR-466i-5p and up-regulating its targets; among them Onecut2, which is the upstream regulator of the MN-specific programming factor Islet-1. In synergy with lncMN2-203, instead the depletion of the co-transcribed miR-325-3p and miR-384-5p was found to mainly sustain proliferation-related factors. These findings indicate the functional relevance of the MN2 locus and contribute to elucidate additional layers of regulation controlling the specificity of motor neuron differentiation.
2021-11-16 | GSE174671 | GEO
Project description:The transition from dividing progenitors to post-mitotic motor neurons (MNs) is orchestrated by a series of events, which are mainly studied at the transcriptional level by analyzing the activity of specific programming transcription factors. Here, we identify a post-transcriptional role of a MN-specific transcriptional unit (MN2) harboring a lncRNA (lncMN2-203) and two miRNAs (miR-325-3p and miR-384-5p) in this transition. Through the use of in vitro mESC differentiation and single-cell sequencing of CRISPR/Cas9 mutants, we demonstrate that lncMN2-203 affects MN differentiation by sponging miR-466i-5p and up-regulating its targets, including several factors involved in neuronal differentiation and function. In parallel, miR-325-3p and miR-384-5p, co-transcribed with lncMN2-203, act by repressing proliferation-related factors. These findings indicate the functional relevance of the MN2 locus and exemplify additional layers of specificity regulation in MN differentiation.
| S-SCDT-EMBOJ-2021-108918 | biostudies-other
Project description:The motor neuron (MN)–hexamer complex consisting of LIM homeobox 3, Islet-1, and nuclear LIM interactor is a key determinant of motor neuron specification and differentiation. To gain insights into the transcriptional network in motor neuron development, we performed a genome-wide ChIP-sequencing analysis and found that the MN–hexamer directly regulates a wide array of motor neuron genes by binding to the HxRE (hexamer response element) shared among the target genes. Interestingly, STAT3-binding motif is highly enriched in the MN–hexamer–bound peaks in addition to the HxRE. We also found that a transcriptionally active form of STAT3 is expressed in embryonic motor neurons and that STAT3 associates with the MN–hexamer, enhancing the transcriptional activity of the MN–hexamer in an upstream signal-dependent manner. Correspondingly, STAT3 was needed for motor neuron differentiation in the developing spinal cord. Together, our studies uncover crucial gene regulatory mechanisms that couple MN–hexamer and STAT-activating extracellular signals to promote motor neuron differentiation in vertebrate spinal cord. To explain our experimental scheme briefly, we are interested in finding target sites for the dimer of transcription factors Isl1 and Lhx3. To mimic the biological activity of Isl1/Lhx3 dimer, we made Isl1-Lhx3 fusion and found that Isl1-Lhx3 has a potent biological activity in multiple systems (i.e. generation of ectopic motor neurons). Then we made ES cell line that induces Flag-tagged Isl1-Lhx3 expression upon Dox treatment. These *mouse* ES cells differentiate to motor neurons (iMN-ESCs) when treated with Dox following EB formation. To identify genomic binding sites of Isl1-Lhx3 (Flag-tagged), we performed ChIP with Flag antibody (pull down of Flag-Isl1-Lhx3) in ES cells treated with Dox. ChIP with Flag antibody in ES cells treated with vehicle (no Dox) was done as a negative control in parallel, and sequenced along with +Dox sample. We have done these experiments twice (two sets).
2013-09-19 | E-GEOD-50993 | biostudies-arrayexpress
Project description:To determine what kind of genes are involved in vocal learning ability, we performed microarray experiments using 3 vocal learning species (zebra finch, budgerigar, Anna's hummingbird) and 2 non-vocal learning species(ring dive, and Japanese quail) from the bird group. All of the animals are male adults. They were isolated over night and had 1hour light exposure at morning. Birds who did not sing were used in this experiment. We used 2-3 animals each species. We used the 12th motor neuron for both vocal learners and non-vocal learners. We used the Supra Spinal motor neuron (ssp) as control area for both groups.
2012-05-30 | E-GEOD-33667 | biostudies-arrayexpress
Project description:The motor neuron (MN)–hexamer complex consisting of LIM homeobox 3, Islet-1, and nuclear LIM interactor is a key determinant of motor neuron specification and differentiation. To gain insights into the transcriptional network in motor neuron development, we performed a genome-wide ChIP-sequencing analysis and found that the MN–hexamer directly regulates a wide array of motor neuron genes by binding to the HxRE (hexamer response element) shared among the target genes. Interestingly, STAT3-binding motif is highly enriched in the MN–hexamer–bound peaks in addition to the HxRE. We also found that a transcriptionally active form of STAT3 is expressed in embryonic motor neurons and that STAT3 associates with the MN–hexamer, enhancing the transcriptional activity of the MN–hexamer in an upstream signal-dependent manner. Correspondingly, STAT3 was needed for motor neuron differentiation in the developing spinal cord. Together, our studies uncover crucial gene regulatory mechanisms that couple MN–hexamer and STAT-activating extracellular signals to promote motor neuron differentiation in vertebrate spinal cord.
2013-09-19 | GSE50993 | GEO
Project description:The transition from dividing progenitors to postmitotic motor neurons (MNs) is orchestrated by a series of events, which are mainly studied at the transcriptional level by analyzing the activity of specific programming transcription factors. Here, we identify a post-transcriptional role of a MN-specific transcriptional unit (MN2) harboring a lncRNA (lncMN2-203) and two miRNAs (miR-325-3p and miR-384-5p) in this transition. Through the use of in vitro mESC differentiation and single-cell sequencing of CRISPR/Cas9 mutants, we demonstrate that lncMN2-203 affects MN differentiation by sponging miR-466i-5p and upregulating its targets, including several factors involved in neuronal differentiation and function. In parallel, miR-325-3p and miR-384-5p, co-transcribed with lncMN2-203, act by repressing proliferation-related factors. These findings indicate the functional relevance of the MN2 locus and exemplify additional layers of specificity regulation in MN differentiation.
| S-EPMC9251839 | biostudies-literature
Project description:To investigate the role of motor neuron autophagy in ALS, we generated mice in which the critical autophagy gene Atg7 was specifically disrupted in motor neurons (Atg7 cKO). We also bred these mice to the SOD1G93A mouse model of ALS. Then we performed RNA sequencing on lumbar spinal cords from these mice to determine how motor neuron autophagy inhibition altered gene expression.
2017-08-10 | GSE100888 | GEO
Project description:Muscular atrophy (SMA) is an autosomal recessive disease causing selective motor neuron death by the loss of telomeric survival motor neuron gene, SMN1. Axonal SMN, a-SMN, is a truncated form of SMN, derived from an alternatively spliced SMN1 gene. (Setola, et. al. 2007 PNAS 104, 1959-1964). The cellular clones expressing a-SMN in a tetracycline-dependent manner were isolated from NSC34 by two-step stable transfection, first with the tetracycline-repressor construct and subsequently with the a-SMN cDNA. To identify novel a-SMN target genes, the transcriptome of several a-SMN clones was analyzed and compared with that of parental cells.
2012-01-07 | E-MEXP-3402 | biostudies-arrayexpress
Project description:We profiled miRNAs from embryonic stem cells to motor neurons derived via RA (retinoic acid) and distinguished different developmental stages by days. Those developmental stages are ESC, Day2, Day3, Day4, and both motor neuron and interneuron with day7. We also provide the fractionated nuclear and cytoplasm miRNA profiling with motor neuron and interneuron respectivey.
2022-12-01 | GSE147828 | GEO