Chx10 consolidates V2a interneuron identity through two distinct gene repression modes
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PROVIDER: PRJNA327230 | ENA |
REPOSITORIES: ENA
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Project description:During development, two cell-types born from closely related progenitor pools often express the identical transcriptional regulators despite their completely distinct characteristics. This phenomenon highlights the necessity of the mechanism that operates to segregate the identities of the two cell-types throughout differentiation after initial fate commitment. To understand this mechanism, we investigated the fate specification of spinal V2a interneurons, which share important developmental genes with motor neurons (MNs). Here we demonstrate that the paired homeodomain factor Chx10 functions as a critical determinant for V2a fate and is required to consolidate V2a identity in postmitotic neurons. Chx10 actively promotes V2a fate, downstream of the LIM-homeodomain factor Lhx3, while concomitantly suppressing MN developmental program by preventing the MN-specific transcription complex from binding and activating MN genes. This dual activity enables Chx10 to effectively separate V2a and MN pathways. Together, our study uncovers a widely applicable gene regulatory principle for segregating related cell fates. RNA samples from Chx10-ESC-derived MNs were prepared for sequencing according to the Illumina protocol, and sequenced on the Illumina HiSeq 2000. We will then compare the transcriptome changes between -Dox (no Chx10) and +Dox (Chx10) in order to identify genes rregulated by Chx10.
2016-07-28 | E-GEOD-83873 | biostudies-arrayexpress
Project description:During development, two cell-types born from closely related progenitor pools often express the identical transcriptional regulators despite their completely distinct characteristics. This phenomenon highlights the necessity of the mechanism that operates to segregate the identities of the two cell-types throughout differentiation after initial fate commitment. To understand this mechanism, we investigated the fate specification of spinal V2a interneurons, which share important developmental genes with motor neurons (MNs). Here we demonstrate that the paired homeodomain factor Chx10 functions as a critical determinant for V2a fate and is required to consolidate V2a identity in postmitotic neurons. Chx10 actively promotes V2a fate, downstream of the LIM-homeodomain factor Lhx3, while concomitantly suppressing MN developmental program by preventing the MN-specific transcription complex from binding and activating MN genes. This dual activity enables Chx10 to effectively separate V2a and MN pathways. Together, our study uncovers a widely applicable gene regulatory principle for segregating related cell fates. ChIP DNA samples from Chx10-ESC-derived MNs were prepared for sequencing according to the Illumina protocol, and sequenced on the Illumina HiSeq 2000. The peak calling was conducted with MACS software (Zhang et al., 2008). MEME-ChIP Suite (Bailey et al., 2009; Machanick and Bailey, 2011) and TOMTOM algorithm (Gupta et al., 2007) was used for motif analysis.
2016-07-28 | E-GEOD-83872 | biostudies-arrayexpress
Project description:During development, two cell-types born from closely related progenitor pools often express the identical transcriptional regulators despite their completely distinct characteristics. This phenomenon highlights the necessity of the mechanism that operates to segregate the identities of the two cell-types throughout differentiation after initial fate commitment. To understand this mechanism, we investigated the fate specification of spinal V2a interneurons, which share important developmental genes with motor neurons (MNs). Here we demonstrate that the paired homeodomain factor Chx10 functions as a critical determinant for V2a fate and is required to consolidate V2a identity in postmitotic neurons. Chx10 actively promotes V2a fate, downstream of the LIM-homeodomain factor Lhx3, while concomitantly suppressing MN developmental program by preventing the MN-specific transcription complex from binding and activating MN genes. This dual activity enables Chx10 to effectively separate V2a and MN pathways. Together, our study uncovers a widely applicable gene regulatory principle for segregating related cell fates.
2016-07-28 | GSE83872 | GEO
Project description:During development, two cell-types born from closely related progenitor pools often express the identical transcriptional regulators despite their completely distinct characteristics. This phenomenon highlights the necessity of the mechanism that operates to segregate the identities of the two cell-types throughout differentiation after initial fate commitment. To understand this mechanism, we investigated the fate specification of spinal V2a interneurons, which share important developmental genes with motor neurons (MNs). Here we demonstrate that the paired homeodomain factor Chx10 functions as a critical determinant for V2a fate and is required to consolidate V2a identity in postmitotic neurons. Chx10 actively promotes V2a fate, downstream of the LIM-homeodomain factor Lhx3, while concomitantly suppressing MN developmental program by preventing the MN-specific transcription complex from binding and activating MN genes. This dual activity enables Chx10 to effectively separate V2a and MN pathways. Together, our study uncovers a widely applicable gene regulatory principle for segregating related cell fates.
2016-07-28 | GSE83873 | GEO
Project description: Not available
| S-EPMC8109239 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2016-07-28 | E-GEOD-83874 | biostudies-arrayexpress
Project description:The spinal cord contains neural networks that enable regionally-distinct motor outputs along the body axis. Nevertheless, it remains unclear how segment-specific motor computations are processed because the cardinal interneuron classes that control motor neurons appear uniform at each level of the spinal cord. V2a interneurons are essential to both fore and hindlimb movements and here we identified two major types that emerge during development: Type-I neurons marked by high Chx10 form recurrent networks with neighboring spinal neurons, and Type-II that downregulate Chx10 and project to supraspinal structures. Type-I and -II V2a interneurons are arrayed in counter-gradients and this network activates different patterns of motor output at cervical and lumbar levels. Single cell RNA-seq revealed Type-I and -II V2a neurons are each comprised of multiple subtypes. Our findings uncover a molecular and anatomical organization of V2a interneurons reminiscent of the orderly way motor neurons are divided into columns and pools.
2018-02-22 | GSE108775 | GEO
Project description:The spinal cord contains neural networks that enable regionally-distinct motor outputs along the body axis. Nevertheless, it remains unclear how segment-specific motor computations are processed because the cardinal interneuron classes that control motor neurons appear uniform at each level of the spinal cord. V2a interneurons are essential to both fore and hindlimb movements and here we identified two major types that emerge during development: Type-I neurons marked by high Chx10 form recurrent networks with neighboring spinal neurons, and Type-II that downregulate Chx10 and project to supraspinal structures. Type-I and -II V2a interneurons are arrayed in counter-gradients and this network activates different patterns of motor output at cervical and lumbar levels. Single cell RNA-seq revealed Type-I and -II V2a neurons are each comprised of multiple subtypes. Our findings uncover a molecular and anatomical organization of V2a interneurons reminiscent of the orderly way motor neurons are divided into columns and pools.
2018-02-22 | GSE108788 | GEO
Project description:Chx10 consolidates V2a interneuron identity through two distinct gene repression modes [RNA-Seq]
| PRJNA327234 | ENA
Project description:Chx10 consolidates V2a interneuron identity through two distinct gene repression modes [ChIP-Seq]
| PRJNA327232 | ENA