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RNA seq profile of adult newborn neurons

ABSTRACT: RNA seq profile of adult newborn neurons

PROVIDER: PRJNA707013 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13863825_1.fastq.gz	Fastqsanger.gz
	SRR13863825_2.fastq.gz	Fastqsanger.gz
	SRR13863826_1.fastq.gz	Fastqsanger.gz
	SRR13863826_2.fastq.gz	Fastqsanger.gz
	SRR13863827_1.fastq.gz	Fastqsanger.gz

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RNA seq profile of adult newborn neurons

Project description:The integration of adult-born neurons in the existent neural circuitry is known to be activity-dependent. To decipher the underlying mechanisms, we genetically manipulated excitability of adult-born cells (via cell-specific overexpression of either Kv1.2 or Kir2.1 K+ channels). Longitudinal in vivo Ca2+ imaging and transcriptome analyses revealed that endogenous but not sensory-driven activity governs migration, morphogenesis, survival, and functional integration of adult-born juxtaglomerular neurons in the mouse olfactory bulb. The proper development of these cells required fluctuations of cytosolic Ca2+ levels, phosphorylation of CREB, and pCREB-mediated gene expression. Attenuating Ca2+ fluctuations via K+ channel overexpression strongly downregulated genes involved in neuronal migration, differentiation, and morphogenesis and upregulated the apoptosis-related genes, thus locking adult-born cells in the vulnerable and immature state. Together, the data identify signaling pathways connecting the endogenous intermittent neuronal activity/Ca2+ fluctuations as well as proper Kv1.2/Kir2.1 K+ channel function to migration, maturation, and survival of adult-born neurons.

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Single cell sequencing of radial glia progeny reveals diversity of newborn neurons in the adult zebrafish brain

Project description:Zebrafish display widespread and pronounced adult neurogenesis, which is fundamental for their regeneration capability after central nervous system injury. However, the cellular identity and the biological properties of adult newborn neurons are elusive for most brain areas. Here, we used short-term lineage tracing of radial glia progeny to prospectively isolate newborn neurons from the her4.1+ radial glia lineage in the homeostatic adult forebrain. Transcriptome analysis of radial glia, newborn neurons and mature neurons using single cell sequencing identified distinct transcriptional profiles including novel markers for each population. Specifically, we detected 2 separate newborn neuron types, which showed diversity of cell fate commitment and location. Further analyses showed homology of these cell types to neurogenic cells in the mammalian brain, identified neurogenic commitment in proliferating radial glia and indicated that glutamatergic projection neurons fate are generated in the adult zebrafish telecephalon. Thus, we prospectively isolated adult newborn neurons from the adult zebrafish forebrain, identified markers for newborn and mature neurons in the adult brain, revealed intrinsic heterogeneity among adult newborn neurons and their homology to mammalian adult neurogenic cell types.

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Div-Seq: Single-nucleus RNA-Seq reveals dynamics of rare adult newborn neurons.

Project description:Single-cell RNA sequencing (RNA-Seq) provides rich information about cell types and states. However, it is difficult to capture rare dynamic processes, such as adult neurogenesis, because isolation of rare neurons from adult tissue is challenging and markers for each phase are limited. Here, we develop Div-Seq, which combines scalable single-nucleus RNA-Seq (sNuc-Seq) with pulse labeling of proliferating cells by 5-ethynyl-2'-deoxyuridine (EdU) to profile individual dividing cells. sNuc-Seq and Div-Seq can sensitively identify closely related hippocampal cell types and track transcriptional dynamics of newborn neurons within the adult hippocampal neurogenic niche, respectively. We also apply Div-Seq to identify and profile rare newborn neurons in the adult spinal cord, a noncanonical neurogenic region. sNuc-Seq and Div-Seq open the way for unbiased analysis of diverse complex tissues.

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Single cell sequencing of radial glia progeny reveals diversity of newborn neurons in the adult zebrafish brain

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Loss of CBP in newborn neurons interferes with synaptic maturation and SRF-dependent neuronal growth

Project description:We used genome-wide sequencing methods to study the consequences of eliminating the CREB-binding protein (CBP) in newborn neurons. We found that CBP-deficient newborn neurons show impaired growth and activity-dependent transcription. In particular, genes downstream of the serum response factor (SRF) and related to neuronal growth and activity-dependent plasticity were affected. The expression of a constitutively active SRF protein with the ability to transactivate target genes in a CBP-independent manner reduced the growth and transcriptional defects associated with CBP ablation.

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