Decoding neuronal composition and ontogeny of individual hypothalamic nuclei

Ma, Tong; Wong, Samuel Zheng Hao; Lee, Bora; Ming, Guo‐li; Song, Hongjun

doi:10.1016/j.neuron.2021.01.026

Cited by 23 publications

(13 citation statements)

References 85 publications

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“…In the hypothalamus, neurons that control body growth [ 5 – 8 ] and energy metabolism [ 13 , 14 ] are mainly located in the ARC nucleus. TBX3, a marker gene specifically expressed in the ARC [ 47 , 48 ], was also specifically and highly expressed in cluster 3 (Fig. 2 F).…”

Section: Resultsmentioning

confidence: 99%

Adamantinomatous craniopharyngioma cyst fluid can trigger inflammatory activation of microglia to damage the hypothalamic neurons by inducing the production of β-amyloid

Ainiwan

Chen

Mao

et al. 2022

J Neuroinflammation

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Introduction The mechanism by which adamantinomatous craniopharyngioma (ACP) damages the hypothalamus is still unclear. Cyst fluid rich in lipids and inflammatory factors is a characteristic pathological manifestation of ACP and may play a very important role in hypothalamic injury caused by tumors. Objective The objective of this study was to construct a reliable animal model of ACP cyst fluid-induced hypothalamic injury and explore the specific mechanism of hypothalamic injury caused by cyst fluid. Methods An animal model was established by injecting human ACP cyst fluid into the bilateral hypothalamus of mice. ScRNA-seq was performed on the mice hypothalamus and on an ACP sample to obtain a complete gene expression profile for analysis. Data verification was performed through pathological means. Results ACP cystic fluid caused growth retardation and an increased obesity index in mice, affected the expression of the Npy, Fgfr2, Rnpc3, Sst, and Pcsk1n genes that regulate growth and energy metabolism in hypothalamic neurons, and enhanced the cellular interaction of Agrp–Mc3r. ACP cystic fluid significantly caused inflammatory activation of hypothalamic microglia. The cellular interaction of CD74–APP is significantly strengthened between inflammatory activated microglia and hypothalamic neurons. Beta-amyloid, a marker of neurodegenerative diseases, was deposited in the ACP tumor tissues and in the hypothalamus of mice injected with ACP cyst fluid. Conclusion In this study, a novel animal model of ACP cystic fluid-hypothalamic injury was established. For the first time, it was found that ACP cystic fluid can trigger inflammatory activation of microglia to damage the hypothalamus, which may be related to the upregulation of the CD74–APP interaction and deposition of β-amyloid, implying that there may be a similar mechanism between ACP cystic fluid damage to the hypothalamus and neurodegenerative diseases.

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Section: Resultsmentioning

confidence: 99%

Adamantinomatous craniopharyngioma cyst fluid can trigger inflammatory activation of microglia to damage the hypothalamic neurons by inducing the production of β-amyloid

Ainiwan

Chen

Mao

et al. 2022

J Neuroinflammation

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“…Upon closer inspection of the difference between clusters 0 and 8, we identified a subset of cells within cluster 8 that expressed NKX2 . 1 , a marker of hypothalamic neurons 39 .…”

Section: Resultsmentioning

confidence: 99%

Enhanced Production of Mesencephalic Dopaminergic Neurons from Lineage-Restricted Human Undifferentiated Stem Cells

Maimaitili

Chen

Febbraro³

et al. 2021

Preprint

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The differentiation of human pluripotent stem cells (hPSCs) into mesencephalic dopaminergic (mesDA) neurons requires a precise combination of extrinsic factors that recapitulates the in vivo environment and timing. Current methods are capable of generating authentic mesDA neurons after long-term culture in vitro; however, when mesDA progenitors are transplanted in vivo, the resulting mesDA neurons are only minor components of the graft. This low yield hampers the broad use of these cells in the clinic. In this study, we genetically modified pluripotent stem cells to generate a novel type of stem cells called lineage-restricted undifferentiated stem cells (LR-USCs), which robustly generate mesDA neurons. LR-USCs are prevented from differentiating into a broad range of nondopaminergic cell types by knocking out genes that are critical for the specification of cells of alternate lineages. Specifically, we target transcription factors involved in the production of spinal cord and posterior hindbrain cell types. When LR-USCs are differentiated under caudalizing condition, which normally give rise to hindbrain cell types, a large proportion adopt a midbrain identity and develop into authentic mesDA neurons. We show that the mesDA neurons are electrophysiologically active, and due to their higher purity, are capable of restoring motor behavior eight weeks after transplantation into 6-hydroxydopamine (6-OHDA)-lesioned rats. This novel strategy improves the reliability and scalability of mesDA neuron generation for clinical use.

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“…On a molecular level, ArcN POMC neurons display a large degree of heterogeneity in terms of expression levels of genes encoding various receptors for classical neurotransmitters, neuropeptides, hormones, or transcription factors (Biglari et al, 2021; Campbell et al, 2017; Lam et al, 2017; Ma et al, 2021). In addition, ~50–75% of ArcN POMC neurons in the mouse are GABAergic, ~10–40% are glutamatergic, and up to 30% express both GABA and glutamatergic synthesizing enzymes (Hentges et al, 2009; Jarvie & Hentges, 2012; Stincic et al, 2018; Wittmann et al, 2013), suggesting dual excitatory and inhibitory functions.…”

Section: Discussionmentioning

confidence: 99%

Ethanol consumption activates a subset of arcuate nucleus pro‐opiomelanocortin (POMC)‐producing neurons: a c‐fos immunohistochemistry study

Hood

Nagy

Leyrer‐Jackson

2022

Physiological Reports

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Ethanol activates various opioid peptide‐containing circuits within the brain that may underlie its motivational and rewarding effects. One component of this circuitry consists of neurons located in the arcuate nucleus (ArcN) of the hypothalamus which express pro‐opiomelanocortin (POMC), an opioid precursor peptide that is cleaved to form bioactive fragments including β‐endorphin and α‐melanocyte stimulating hormone. In this study, we sought to determine if ethanol intake activates ArcN POMC neurons as measured by expression of the immediate early gene c‐fos. Male and female POMC‐EGFP mice underwent drinking‐in‐the‐dark (DID) procedures for 3 consecutive days (2 h/day) and were allowed to consume either ethanol (20% v/v), saccharin (0.2% w/v), or water. On the fourth day of DID procedures, animals were allowed to consume their respective solutions for 20 min, and 1 h following the session brains were harvested and processed for c‐fos immunohistochemistry and co‐localization with EGFP. Our results indicate that ethanol intake activates a subset (~15–20%) of ArcN POMC neurons, whereas saccharin or water intake activates significantly fewer (~5–12%) of these neurons. The percent of activated POMC neurons did not correlate with blood ethanol levels at the time of tissue collection, and activation appeared to be distributed throughout the rostrocaudal axis of the ArcN. No sex differences were observed in the degree of neuronal activation across drinking solutions. These findings indicate a preferential activation of ArcN POMC neurons by ethanol consumption, strengthening the notion that ethanol activates endogenous opioid systems in the brain which may underlie its motivational properties.

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Decoding neuronal composition and ontogeny of individual hypothalamic nuclei

Cited by 23 publications

References 85 publications

Adamantinomatous craniopharyngioma cyst fluid can trigger inflammatory activation of microglia to damage the hypothalamic neurons by inducing the production of β-amyloid

Adamantinomatous craniopharyngioma cyst fluid can trigger inflammatory activation of microglia to damage the hypothalamic neurons by inducing the production of β-amyloid

Enhanced Production of Mesencephalic Dopaminergic Neurons from Lineage-Restricted Human Undifferentiated Stem Cells

Ethanol consumption activates a subset of arcuate nucleus pro‐opiomelanocortin (POMC)‐producing neurons: a c‐fos immunohistochemistry study

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