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    Home > Active Ingredient News > Study of Nervous System > Nat Comm | Wu Qingfeng's team reveals that hypothalamic extension cells have the duality of angels and demons

    Nat Comm | Wu Qingfeng's team reveals that hypothalamic extension cells have the duality of angels and demons

    • Last Update: 2021-05-09
    • Source: Internet
    • Author: User
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    The mammalian hypothalamus is the advanced center of the brain that regulates visceral activity, and participates in important body physiological functions such as regulating body temperature, food intake, water balance, blood sugar and endocrine activity.

    The median eminence (ME) located at the bottom of the third ventricle of the hypothalamus is a key part of the brain where there is no blood-brain barrier, and it plays a vital role in the communication between the body and the brain.

    In the past, it was thought that there are a special group of glial cells in the hypothalamic ME, namely tanycytes, which may play the role of neural stem cells.

    The nerve cell population participates in the regulation of multiple functions, including endocrine output, blood-derived molecular input, metabolic balance and body aging, etc.
    , and plays a pivotal role in the maintenance of mammalian body homeostasis.

    At present, the cellular characteristics, self-renewal and differentiation potential of the stretched cells in the ME area and their mechanisms are still unclear.
    In-depth research is needed to explore the potential of stretched cells to provide an important basis for the hypothalamic stretched cells to maintain endocrine balance and metabolic homeostasis.

    Recently, the team of researcher Wu Qingfeng from the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences published an online research paper on Nature Communications entitled: Hypothalamic Rax+ tanycytes contribute to tissue repair and tumorigenesis upon oncogene activation in mice.

    The study found that the Rax+ stretch cells in the hypothalamic ME are in a resting state under normal physiological conditions, but turn into an active state after nerve injury, quickly enter the cell cycle and perform self-renewal and regeneration; more importantly, the introduction of Braf The original cancer mutation can cause Rax+ stretch cells to transform into actively dividing tumor cells, driving tumor formation.
    This study clearly revealed the cellular origin of papillary craniopharyngiomas.This shows that the hypothalamic stretch cells have an angelic aspect, that is, self-renewing and regenerative, and also have a devilish aspect, that is, the malignant potential of producing tumors.

    In order to explore the molecular characteristics of stretched cells in ME, the researchers performed microdissection of mouse ME and mapped its molecular expression profile through single-cell transcriptome sequencing.

    Through bioinformatics analysis, ME cells were divided into 10 cell populations, including stretched cells, neurons, oligodendrocytes (OPCs), etc.

    The researchers first confirmed that Rax is a molecular marker of ME stretched cells, and revealed Scn7a, Col25a1 and Mia as their specific markers, and verified the expression of related genes in stretched cells using smFISH technology.

    Actively dividing cells in ME can control the energy balance of the whole body, but whether stretched cells have mitotic activity is still controversial.

    In order to verify the mitotic activity of Rax+ stretched cells, the researchers used the Rax-CreERT2::Ai14 tool mouse to trace the lineage of Rax+ cells and found that Rax+ stretched cells are resting cells under normal physiological conditions.

    After nerve injury, Rax+ stretched cells quickly enter the cell cycle and undergo self-renewal, regeneration and differentiation, contributing to tissue repair after injury.

    Key signaling pathways play a very important role in the process of stem cells maintaining their resting and activated states.
    In order to explore the mechanism by which Rax+ stretched cells maintain themselves and mediate tissue repair, researchers have found that Rax+ expands through single-cell transcriptome data analysis.
    Igf1r receptor is specifically and highly expressed in cells.

    The lack of Igf1r in Rax+ stretch cells leads to a significant decrease in the number of stretch cells, which affects their own maintenance and leads to damage to tissue repair after injury, revealing that Igf1 signaling pathway is necessary for tissue repair after injury.

    Under normal circumstances, somatic stem cells can not only maintain their own dryness and tissue homeostasis after injury, but also have the potential for carcinogenic transformation, but the tumorigenic ability of stretched cells has never been reported.

    Clinically, craniopharyngioma is a benign but aggressive intracranial tumor that occurs between the hypothalamus and pituitary gland and is divided into enamel type and papillary type.

    Among them, papillary craniopharyngioma has a higher incidence in adults and is often driven by BrafV600E somatic mutations.

    Previous studies have found that the expression of BrafV600E in neural precursor cells is not enough to cause tumors.

    But unexpectedly, the introduction of BrafV600E mutation in Rax+ stretched cells can observe obvious tumorigenesis in ME after 2 months of induction.
    At the same time, the immunofluorescence staining of reporter mice showed that the tumors did originate from Rax+ stretched cells.
    , And show different characteristics from glioma.

    The anatomical location, gene mutation and pathological characteristics of this tumor are very similar to papillary craniopharyngiomas, suggesting that the Rax+ stretch cells of the hypothalamus may be the origin cells of papillary craniopharyngiomas.

    In summary, the Rax+ stretch cells of the hypothalamus are largely in a resting state.
    When nerves are injured, they can transition from a resting state to an active state, thereby achieving tissue regeneration.

    It needs to stretch the Igf1r signal in cells during the process of tissue repair.

    At the same time, Rax+ stretch cells can be transformed into active tumor cells and develop into human papillary craniopharyngioma-like tumors after introducing the BrafV600E mutation, indicating that Rax+ stretch cells have tumorigenic potential and may be the origin cells of papillary craniopharyngiomas .

    This study reveals the resting properties of stretched cells and their regenerative and tumorigenic potential (below), which will help manipulate the biological properties of Rax+ stretched cells to regulate hypothalamic function, and study the pathogenesis and mechanisms of craniopharyngiomas.
    Targeted therapy provides new insights.

    Hypothalamus Rax+ stretch cell regeneration and tumorigenic potential model.

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