Excitatory Neuron-Derived Interleukin-34 Controls Cortical Developmental Microglia Function
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1230265 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR32537318_1.fastq.gz | Fastqsanger.gz | |||
| SRR32537318_2.fastq.gz | Fastqsanger.gz | |||
| SRR32537319_1.fastq.gz | Fastqsanger.gz | |||
| SRR32537319_2.fastq.gz | Fastqsanger.gz | |||
| SRR32537320_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 60 |
Similar Datasets
Project description:Neuron-microglia interactions dictate the development of neuronal circuits in the brain. However, the factors that support and broadly regulate these processes across developmental stages are largely unknown. Here, we find that IL34, a neuron-derived cytokine, is upregulated in development and plays a critical role in supporting and maintaining neuroprotective, mature microglia in the anterior cingulate cortex (ACC) of mice. We show that IL34 mRNA and protein is upregulated in neurons in the second week of postnatal life and that this increase coincides with increases in microglia number and expression of mature, homeostatic markers, e.g., TMEM119. We also found that IL34 mRNA is higher in excitatory (compared to inhibitory) neurons. Global genetic KO of IL34 reduced microglia numbers and prevented the functional maturation of microglia, and excitatory-neuron specific KO of IL34 similarly impacted microglia and increased aberrant microglial phagocytosis of excitatory thalamocortical synapses in the ACC. Acute, low dose blocking of IL34 at postnatal day (P)15 in mice decreased microglial TMEM119 protein and also increased microglial phagocytosis of excitatory thalamocortical synapses during an inappropriate time in development. In contrast, viral overexpression of IL34 early in life (P1-P8) caused early maturation of microglia and prevented microglial phagocytosis of thalamocortical synapses during the appropriate neurodevelopmental refinement window. Taken together, these findings establish IL34 as a key regulator of neuron microglia crosstalk in postnatal brain development, controlling both microglial maturation and synapse engulfment.
2025-04-14 | GSE290856 | GEO
Project description:MYT1L deficiency impairs excitatory neuron trajectory during cortical development
| PRJNA1091594 | ENA
Project description:MYT1L deficiency impairs excitatory neuron trajectory during cortical development [P21]
| PRJNA1091601 | ENA
Project description:MYT1L deficiency impairs excitatory neuron trajectory during cortical development [P1]
| PRJNA1144958 | ENA
Project description:MYT1L deficiency impairs excitatory neuron trajectory during cortical development [E14]
| PRJNA1091600 | ENA
Project description:Human CLOCK enhances cognitive flexibility by altering cortical excitatory neuron function
| PRJNA932429 | ENA
Project description:Mutations that reduce the function of MYT1L, a neuron-specific transcription factor, are associated with a syndromic neurodevelopmental disorder. Furthermore, MYT1L is routinely used as a pro-neural factor in fibroblast-to-neuron transdifferentiation. MYT1L has been hypothesized to play a role in the trajectory of neuronal specification and subtype specific maturation, but this hypothesis has not been directly tested, nor is it clear which neuron types are most impacted by MYT1L loss. In this study, we profiled 412,132 nuclei from the forebrains of wild-type and MYT1L-deficient mice at three developmental stages: E14 at the peak of neurogenesis, P1 when neurons in the six cortical layers have been born, and P21 when neurogenesis is complete and neurons are maturing, to examine the role of MYT1L levels in the trajectory of neuronal development. We found that MYT1L deficiency significantly disrupted the relative proportions of cortical excitatory neurons. Changes in gene expression were concentrated in excitatory neurons, suggesting that transcriptional effects of MYT1L deficiency are largely due to disruption of neuronal maturation programs. Most effects on gene expression were cell autonomous and persistent through development. In addition, while MYT1L can both activate and repress gene expression, the repressive effects were most sensitive to haploinsufficiency, and thus more likely mediate MYT1L syndrome. These findings illuminate the intricate role of MYT1L in orchestrating gene expression dynamics during neuronal development, providing insights into the molecular underpinnings of MYT1L syndrome.
2024-08-12 | GSE274102 | GEO
Project description:Mutations that reduce the function of MYT1L, a neuron-specific transcription factor, are associated with a syndromic neurodevelopmental disorder. Furthermore, MYT1L is routinely used as a pro-neural factor in fibroblast-to-neuron transdifferentiation. MYT1L has been hypothesized to play a role in the trajectory of neuronal specification and subtype specific maturation, but this hypothesis has not been directly tested, nor is it clear which neuron types are most impacted by MYT1L loss. In this study, we profiled 412,132 nuclei from the forebrains of wild-type and MYT1L-deficient mice at three developmental stages: E14 at the peak of neurogenesis, P1 when neurons in the six cortical layers have been born, and P21 when neurogenesis is complete and neurons are maturing, to examine the role of MYT1L levels in the trajectory of neuronal development. We found that MYT1L deficiency significantly disrupted the relative proportions of cortical excitatory neurons. Changes in gene expression were concentrated in excitatory neurons, suggesting that transcriptional effects of MYT1L deficiency are largely due to disruption of neuronal maturation programs. Most effects on gene expression were cell autonomous and persistent through development. In addition, while MYT1L can both activate and repress gene expression, the repressive effects were most sensitive to haploinsufficiency, and thus more likely mediate MYT1L syndrome. These findings illuminate the intricate role of MYT1L in orchestrating gene expression dynamics during neuronal development, providing insights into the molecular underpinnings of MYT1L syndrome.
2024-04-11 | GSE262366 | GEO
Project description:Mutations that reduce the function of MYT1L, a neuron-specific transcription factor, are associated with a syndromic neurodevelopmental disorder. Furthermore, MYT1L is routinely used as a pro-neural factor in fibroblast-to-neuron transdifferentiation. MYT1L has been hypothesized to play a role in the trajectory of neuronal specification and subtype specific maturation, but this hypothesis has not been directly tested, nor is it clear which neuron types are most impacted by MYT1L loss. In this study, we profiled 412,132 nuclei from the forebrains of wild-type and MYT1L-deficient mice at three developmental stages: E14 at the peak of neurogenesis, P1 when neurons in the six cortical layers have been born, and P21 when neurogenesis is complete and neurons are maturing, to examine the role of MYT1L levels in the trajectory of neuronal development. We found that MYT1L deficiency significantly disrupted the relative proportions of cortical excitatory neurons. Changes in gene expression were concentrated in excitatory neurons, suggesting that transcriptional effects of MYT1L deficiency are largely due to disruption of neuronal maturation programs. Most effects on gene expression were cell autonomous and persistent through development. In addition, while MYT1L can both activate and repress gene expression, the repressive effects were most sensitive to haploinsufficiency, and thus more likely mediate MYT1L syndrome. These findings illuminate the intricate role of MYT1L in orchestrating gene expression dynamics during neuronal development, providing insights into the molecular underpinnings of MYT1L syndrome.
2024-04-11 | GSE262364 | GEO
Project description:The cerebral cortex is a cellularly-complex structure comprised of a rich diversity of neuronal and glial cell types. Cortical neurons can be broadly categorized into two classes—glutamatergic excitatory neurons and GABAergic inhibitory interneurons. Previous developmental studies in rodents have led to the prevailing model that while excitatory neurons are born from progenitors located in the cortex, cortical interneurons are born from a separate population of progenitors located outside of the developing cortex in the ganglionic eminences1-5. However, the developmental potential of human cortical progenitors has not been thoroughly explored. Here we show that in addition to excitatory neurons and glia, human cortical progenitors are also capable of producing GABAergic neurons with the transcriptional characteristics and morphologies of cortical interneurons. By developing a cellular barcoding tool called “ScRNAseq-compatible Tracer for Identifying Clonal Relationships” (STICR), we were able to perform clonal lineage tracing of 1912 primary human cortical progenitors from six specimens and capture both the transcriptional identities and clonal relationships of their resulting progeny. A subpopulation of cortically-born GABAergic neurons were transcriptionally similar to cortical interneurons born from the caudal ganglionic eminence and these cells were frequently related to excitatory neurons and glia. Thus, our results demonstrate that individual human cortical progenitors can generate both excitatory neurons and cortical interneurons, providing a new framework for understanding the origins of neuronal diversity in the human cortex.
2021-11-06 | GSE187875 | GEO