Single cell RNAseq analysis in embryonic spinal cords to profile transcriptomes in control and Jmjd3cKO motor neurons.
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE156609 | GEO | 2022/01/05
REPOSITORIES: GEO
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Project description:Spinal muscular atrophy (SMA) is a neurodegenerative disease which exhibits selective motor neuron death caused by a ubiquitous deficiency of the survival motor neuron (SMN) protein. It remains unclear how the ubiquitous reduction of SMN lead to death in selective motor neuron pools. Medial motor neuron columns (MMC) are vulnerable, whereas lateral motor columns (LMC) are resistant to motor neuron death in SMA. Here we performed microarray and pathway analysis comparing cholera toxin subunit B (CTb) labeled vulnerable MMC and resistant LMC of pre-symptomatic SMA with corresponding motor neuron columns of control mice to identify pathways involved in selective motor neuron death in SMA. WT is FVB. SMN is Delta7 (SMNΔ7;SMN2;Smn-) on a FVB background.
2017-12-12 | GSE81245 | GEO
Project description:Human pluripotent stem cells are a promising source of diverse cells for developmental studies, cell transplantation, disease modeling, and drug testing. However, their widespread use even for intensely studied cell types like spinal motor neurons, is hindered by the long duration and low yields of existing protocols for in vitro differentiation and by the molecular heterogeneity of the populations generated. We report a combination of small molecules that induce up to 50% motor neurons within 3 weeks from human pluripotent stem cells with defined subtype identities that are relevant to neurodegenerative diseases. Despite their accelerated differentiation, motor neurons expressed combinations of HB9, ISL1 and column-specific markers that mirror those observed in vivo in human fetal spinal cord. They also exhibited spontaneous and induced activity, and projected axons towards muscles when grafted into developing chick spinal cord. Strikingly, this novel protocol preferentially generates motor neurons expressing markers of limb-innervating lateral motor column motor neurons (FOXP1+/LHX3-). Access to high-yield cultures of human limb-innervating motor neuron subtypes will facilitate in-depth study of motor neuron subtype-specific properties, disease modeling, and development of large-scale cell-based screening assays. We analyze 3 samples including 2 positive samples and 1 negative sample. Descriptions are as follow: a) Positive Sample 1: SHH-derived, day 21 GFP-high FACS purified motor neurons.b) Positive Sample 2: S+P-derived, day 21 GFP-high FACS purified motor neurons. c) Negative: S+P condition, day 21 no GFP FACS purified motor neurons
2013-02-06 | E-GEOD-41795 | biostudies-arrayexpress
Project description:[original Title] Rapid and synchronous clearance of PcG histone modifications from Hox genes anticipates motor neuron differentiation. Hox genes are expressed in patterns that are spatially and temporally collinear with their chromosomal organization. This feature is an evolutionarily conserved hallmark of embryonic development, and in vertebrates it is critical, among others, for the specification of motor neuron subtypes and the wiring of sensory-motor circuits. We show here that the differentiation of motor neurons from stem cells is accompanied by a synchronous, domain-wide clearance of M-bM-^@M-^\repressiveM-bM-^@M-^] Polycomb (PcG)-dependent histone methylation from Hox gene chromatin domains. These findings argue against the idea, advanced recently, that the collinear dynamics of Hox gene expression invariably reflects the progressive clearance of repressive chromatin modifications. The rapid establishment of stable chromatin domains in response to a transient patterning signal likely serves as a molecular correlate of enduring rostro-caudal neural identity, which underlies the specification of postmitotic motor neuron subtype diversity and neuronal circuit assembly. The differentiation of ventral motor neurons is induced by treating embryonic stem cell cultures with retinoic acid and hedgehog agonist. Here, ChIP-chip using a custom Agilent array is used to profile the occupancy of H3K27me3, H3K4me3, and H3K79me2 at various defined stages during the differentiation process.
2013-07-04 | E-GEOD-19447 | biostudies-arrayexpress
Project description:The pMN domain is a restricted domain in the ventral spinal cords, defined by the expression of olig2 gene. The fate determination of pMN progenitors is highly temporally and spatially regulated, with motor neurons and oligodendrocyte progenitor cells (OPCs) developing sequentially. Insight into the heterogeneity and molecular programs of pMN progenitors is currently lacking. With the zebrafish model, we identified multiple states of neural progenitors using single-cell sequencing: proliferating progenitors, common progenitors for both motor neurons and OPCs, and restricted precursors for either motor neurons or OPCs. We found specific molecular programs for neural progenitor fate transition, and manipulations of representative genes in the motor neuron or OPC lineage confirmed their critical role in cell fate determination. Deciphering progenitor heterogeneity and molecular mechanisms for these transitions will elucidate the formation of complex neuron-glia networks in the central nervous system during development, and understand the basis of neurodevelopmental disorders.
2022-08-20 | GSE179096 | GEO
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.
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Project description:Human pluripotent stem cells are a promising source of diverse cells for developmental studies, cell transplantation, disease modeling, and drug testing. However, their widespread use even for intensely studied cell types like spinal motor neurons, is hindered by the long duration and low yields of existing protocols for in vitro differentiation and by the molecular heterogeneity of the populations generated. We report a combination of small molecules that induce up to 50% motor neurons within 3 weeks from human pluripotent stem cells with defined subtype identities that are relevant to neurodegenerative diseases. Despite their accelerated differentiation, motor neurons expressed combinations of HB9, ISL1 and column-specific markers that mirror those observed in vivo in human fetal spinal cord. They also exhibited spontaneous and induced activity, and projected axons towards muscles when grafted into developing chick spinal cord. Strikingly, this novel protocol preferentially generates motor neurons expressing markers of limb-innervating lateral motor column motor neurons (FOXP1+/LHX3-). Access to high-yield cultures of human limb-innervating motor neuron subtypes will facilitate in-depth study of motor neuron subtype-specific properties, disease modeling, and development of large-scale cell-based screening assays.
2013-02-06 | GSE41795 | GEO
Project description:The neocortex contains an unparalleled diversity of neuronal subtypes responsible for complex behavior. Each cortical neuron has distinct traits, which are developmentally acquired under the control of batteries of neuron subtype-specific and pan-neuronal genes. The cis-regulatory logic that orchestrates the coordinated regulation of each unique combination of genes is not known for any class of neurons of the neocortex. We report that Fezf2, a transcription factor able to induce defining features of corticospinal motor neurons (CSMN), associates with the proximal promoters and regulates expression of series of CSMN signature genes. Fezf2 targets are functionally relevant as demonstrated by the finding that Fezf2 governs expression of the axon guidance receptor EphB1 to execute the ipsilateral extension of the corticospinal tract. Our data indicate that co-regulated expression of neuron subtype-specific gene batteries by a common transcription factor is one component of the regulatory logic responsible for the establishment of CSMN identity.
2014-07-06 | GSE46707 | GEO