Ontogenetic rules for the molecular diversification of hypothalamic neurons

Benevento, Marco; Hökfelt, Tomas; Harkany, Tibor

doi:10.1038/s41583-022-00615-3

Cited by 15 publications

(13 citation statements)

References 232 publications

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“…We also note three intermediate progenitor populations including two ASCL1 + populations and one NEUROD2 + population similar to those reported previously by Zhang et al. ( 16 , 47 ). In Zhou et al.…”

Section: Discussionsupporting

confidence: 90%

“…Within our prenatal samples, we observe sequential formation of all cell types expected within the hypothalamus. These originate from several progenitor populations that resemble those described previously (16,47,53). On the basis of the gene expression profile, our qRGC cluster is analogous to the homonymous cluster in Zhang et al (47), the clusters HPC_1-3 and HPC_1-4 reported in Zhou et al (53).…”

Section: Discussionsupporting

confidence: 79%

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Single-cell genomics reveals region-specific developmental trajectories underlying neuronal diversity in the human hypothalamus

Herb,

Glover,

Bhaduri

et al. 2023

Sci. Adv.

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The development and diversity of neuronal subtypes in the human hypothalamus has been insufficiently characterized. To address this, we integrated transcriptomic data from 241,096 cells (126,840 newly generated) in the prenatal and adult human hypothalamus to reveal a temporal trajectory from proliferative stem cell populations to mature hypothalamic cell types. Iterative clustering of the adult neurons identified 108 robust transcriptionally distinct neuronal subtypes representing 10 hypothalamic nuclei. Pseudotime trajectories provided insights into the genes driving formation of these nuclei. Comparisons to single-cell transcriptomic data from the mouse hypothalamus suggested extensive conservation of neuronal subtypes despite certain differences in species-enriched gene expression. The uniqueness of hypothalamic neuronal lineages was examined developmentally by comparing excitatory lineages present in cortex and inhibitory lineages in ganglionic eminence, revealing both distinct and shared drivers of neuronal maturation across the human forebrain. These results provide a comprehensive transcriptomic view of human hypothalamus development through gestation and adulthood at cellular resolution.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 79%

Single-cell genomics reveals region-specific developmental trajectories underlying neuronal diversity in the human hypothalamus

Herb,

Glover,

Bhaduri

et al. 2023

Sci. Adv.

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“…These two regions are known to project to one another 4,19,54 , with substantial connectivity already documented at P10 22,55 . Strikingly, NeuronChat identified denser putative inter-connectivity at P10 than at P65 (Fig 3s-t These changes may indicate both pruning of exuberant connectivity between P10 and P65, as well as extensive neuropeptidergic signaling in developmental processes, as documented in other brain regions 56,57 . Further, cell types involved in social behavior and homeostatic control appear more inter-connected, at least via neuropeptides, at P10 than at P65, consistent with a higher reliance on social interactions for homeostatic needs early in life 58 .…”

Section: Developmental Changes In Poa Signaling Networkmentioning

confidence: 75%

Sensory Input, Sex, and Function Shape Hypothalamic Cell Type Development

Kaplan,

Logeman,

Zhang

et al. 2024

Preprint

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Mammalian behavior and physiology undergo dramatic changes in early life. Young animals rely on conspecifics to meet their homeostatic needs, until weaning and puberty initiate nutritional independence and sex-specific social interactions, respectively. How neuronal populations regulating homeostatic functions and social behaviors develop and mature during these transitions remains unclear. We used paired transcriptomic and chromatin accessibility profiling to examine the developmental trajectories of neuronal populations in the hypothalamic preoptic region, where cell types with key roles in physiological and behavioral control have been identified. These data reveal a remarkable diversity of developmental trajectories shaped by the sex of the animal, and the location and behavioral or physiological function of the corresponding cell types. We identify key stages of preoptic development, including the perinatal emergence of sex differences, postnatal maturation and subsequent refinement of signaling networks, and nonlinear transcriptional changes accelerating at the time of weaning and puberty. We assessed preoptic development in various sensory mutants and find a major role for vomeronasal sensing in the timing of preoptic cell type maturation. These results provide novel insights into the development of neurons controlling homeostatic functions and social behaviors and lay ground for examining the dynamics of these functions in early life.

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“…3a) (See also companion papers 16,17 ). Additionally, the hypothalamus is comprised of many distinct subregions and nuclei, each with unique functions and contributions to innate behaviors such as aggression, mating and feeding 18 . The hypothalamus therefore serves as an excellent use case for our data set to further examine the relationships between neuronal cell types as defined by their transcriptional and epigenomic signatures, their projection patterns, and their spatial organization.…”

Section: Epi-retro-seq Of Hypothalamic Projection Neurons and Integra...mentioning

confidence: 99%

Brain-wide Correspondence Between Neuronal Epigenomics and Long-Distance Projections

Zhou

Zhang

et al. 2023

Preprint

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Single-cell genetic and epigenetic analyses parse the brain′s billions of neurons into thousands of ″cell type″ clusters, each residing in different brain structures. Many of these cell types mediate their unique functions by virtue of targeted long-distance axonal projections to allow interactions between specific cell types. Here we have used Epi-Retro-Seq to link single cell epigenomes and associated cell types to their long-distance projections for 33,034 neurons dissected from 32 different source regions projecting to 24 different targets (225 source→target combinations) across the whole mouse brain. We highlight uses of this large data set for interrogating both overarching principles relating projection cell types to their transcriptomic and epigenomic properties and for addressing and developing specific hypotheses about cell types and connections as they relate to genetics. We provide an overall synthesis of the data set with 926 statistical comparisons of the discriminability of neurons projecting to each target for every dissected source region. We integrate this dataset into the larger, annotated BICCN cell type atlas composed of millions of neurons to link projection cell types to consensus clusters. Integration with spatial transcriptomic data further assigns projection-enriched clusters to much smaller source regions than afforded by the original dissections. We exemplify these capabilities by presenting in-depth analyses of neurons with identified projections from the hypothalamus, thalamus, hindbrain, amygdala, and midbrain to provide new insights into the properties of those cell types, including differentially expressed genes, their associated cis-regulatory elements and transcription factor binding motifs, and neurotransmitter usage.

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Ontogenetic rules for the molecular diversification of hypothalamic neurons

Cited by 15 publications

References 232 publications

Single-cell genomics reveals region-specific developmental trajectories underlying neuronal diversity in the human hypothalamus

Single-cell genomics reveals region-specific developmental trajectories underlying neuronal diversity in the human hypothalamus

Sensory Input, Sex, and Function Shape Hypothalamic Cell Type Development

Brain-wide Correspondence Between Neuronal Epigenomics and Long-Distance Projections

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