Analysis of gene expression signatures for Litchi knockout during motor neuron differentiation
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE248380 | GEO | 2024/03/11
REPOSITORIES: GEO
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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: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:Combinatorial transcription codes generate the myriad of cell types during development, and thus likely provide crucial insights into directed differentiation of stem cells to a specific cell type. The LIM-complex composed of Isl1 and Lhx3 directs the specification of spinal motor neurons (MNs) in embryos. Here, we report that Isl1-Lhx3, a LIMcomplex-mimicking fusion, induces a signature of MN transcriptome and concomitantly suppresses interneuron differentiation programs, thereby serving as a potent and specific inducer of MNs in stem cells. We show that an equimolar ratio of Isl1 and Lhx3 and the LIM-domain of Lhx3 are crucial for generating MNs without upregulating interneuron genes. These led us to design Isl1-Lhx3, which maintains the desirable 1:1 ratio of Isl1 and Lhx3 and the LIM-domain of Lhx3. Isl1-Lhx3 drives MN differentiation with high specificity and efficiency in the spinal cord and embryonic stem cells, bypassing the need for sonic hedgehog. RNA-seq analysis revealed that Isl1-Lhx3 induces the expression of a battery of MN genes that control various functional aspects of MNs, while suppressing key interneuron genes. Our studies uncover a highly efficient method for directed MN generation and MN gene networks. Our results also demonstrate a general strategy of utilizing embryonic transcription complexes for producing specific cell types from stem cells. Examine the RNA expression profiles of inducible motor neurons-embryonic stem cells (iMN-ESCs) with or without Dox treatment, with biological duplicates.
2012-02-03 | E-GEOD-35510 | 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:Endurance exercise promotes skeletal muscle vascularization, oxidative metabolism, fiber-type switching, and neuromuscular junction integrity. Importantly, the metabolic and contractile properties of the muscle fiber must be coupled to the identity of the innervating motor neuron (MN). Here, we show that muscle-derived neurturin (NRTN) acts on muscle fibers and MNs to couple their characteristics. Using a muscle-specific NRTN transgenic mouse (HSA-NRTN) and RNA-sequencing of MN somas, we observed that retrograde NRTN signaling promotes a shift towards a slow MN identity. In muscle, NRTN increased capillary density, oxidative capacity, and induced a transcriptional reprograming favoring fatty acid metabolism over glycolysis. This combination of effects on muscle and MNs, makes HSA-NRTN mice lean with remarkable exercise performance and motor coordination. Interestingly, HSA-NRTN mice largely recapitulate the phenotype of mice with muscle-specific expression of its upstream regulator PGC-1ɑ1. This work identifies NRTN as a myokine that couples muscle oxidative capacity to slow MN identity.
2021-11-30 | GSE180266 | GEO
Project description:Suz12(Bgal/Bgal) ESCs express a truncated form of Suz12 fused to Beta-galactosidase. These cells maintain a reduced level of H3K27me3 despite this mutation to a core component of PRC2, unlike Eed-/- ESCs whose H3K27me3 is ablated. This data shows the concomitant changes in H3K4me3 levels in these cells. An ESC line mutant in Suz12, a core component of Polycomb Repressive Complex 2, was assessed for H3K4me3 by ChIP-seq, as compared to a wild type ESC line, as well as both lines subjected to in vitro differentiation down the Spinal Motor Neuron pathway.
2014-11-17 | E-GEOD-61248 | biostudies-arrayexpress
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:In the embryonic spinal cord, motor neurons diversify into different subsets characterized by distinct molecular identity, localization and connectivity. However, the factors that control MN diversification remain poorly known. To identify genes downstream of Onecut transcription factors in motor neurons that may contribute to motor neuron diversification, we performed a RNA-sequencing comparison of control and of OC-deficient motor neuron transcriptome at embryonic day 10.5.
2019-12-13 | GSE141949 | GEO
Project description:Here we describe a conserved motor neuron specific long non-coding RNA, Lhx1os, whose knock-out in mice produces motor impairment and post-natal reduction of mature motor neurons (MNs). The endoplasmic reticulum (ER)-stress response pathway resulted specifically altered with the downregulation of factors involved in the Unfolded Protein Response (UPR). Lhx1os was found to bind the ER-associated PDIA3 disulfide isomerase and to affect the expression of the same set of genes controlled by this protein, indicating that the two factors act in conjunction to modulate the UPR. Altogether, the observed phenotype and function of Lhx1os indicate its important role in the control of MN homeostasis and function.
2022-12-20 | GSE189904 | GEO