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Source: iNature (ID: Plant_ihuman) iNature hypothalamus contains amazing heterogeneous neurons, which can regulate endocrine, autonomic and behavioral functions.
However, its molecular development trajectory and the origin of neuronal diversity are still unclear.
On April 21, 2021, Qingfeng Wu's team from the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences published a research paper titled "Cascade diversification directs generation of neuronal diversity in the hypothalamus" in Cell Stem Cell online.
The research introduced the research paper from Rax + The transcriptome of 43261 cells in the hypothalamic neuroepithelium is used to map the development of mouse hypothalamus and the trajectory of firing glial cells (RGC), intermediate progenitor cells (IPC), newborn neurons and peptidergic neurons.
The study showed that RGCs adopt conservative strategies for pluripotent differentiation, but they generate Ascl1 + and Neurog2 + IPC.
Cloning analysis further proved that a single RGC can produce multiple neuronal subtypes.
Studies have shown that multiple cell types along the lineage hierarchy promote the diversification of the fate of hypothalamic neurons in a gradual manner, which suggests a cascading diversification model that deconstructs the origin of neuronal diversity.
In conclusion, the study also determined the embryonic origin of the regulators of postpartum monocytes and designated neuron subtypes, which further provides valuable insights into hypothalamic plasticity and gains in hypothalamic diseases such as anorexia, narcolepsy and insomnia.
Insights provide development prospects.In addition, on April 16, 2021, Wu Qingfeng and other teams from the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences published a research paper entitled "Hypothalamic Rax + tanycytes contribute to tissue repair and tumorigenesis upon oncogene activation in mice" in Nature Communications.
The study combined single-cell transcriptome sequencing, cell lineage tracking, single-molecule in situ hybridization and other technologies to reveal that most of the Rax-positive stretched cells in mouse ME are in a quiescent state, but quickly enter the cell cycle for self-renewal and regeneration after nerve injury .
Under mechanical injury conditions, tissue repair requires activation of the Igf1r signaling pathway in stretched cells.
In addition, the activation of Braf's proto-oncogene is sufficient to transform Rax-positive stretched cells into proliferating tumor cells, and eventually develop into papillary craniopharyngioma-like tumors.
Together, these findings reveal the regeneration and tumorigenic potential of stretched cells.
This study explored the characteristics of stretch cells in depth, which will help us manipulate the biological characteristics of stretch cells to regulate hypothalamic function, and explore the pathogenesis and diagnosis and treatment of clinically relevant tumors.
Understanding the mechanism of brain development requires a systematic investigation of neural progenitor cell types, their lineage specifications, and the development and maturation of neurons after mitosis.
Cumulative evidence based on single-cell transcriptomics analysis revealed the transcriptional heterogeneity of cortical neural progenitor cells, their temporal patterns, and the differentiation trajectory of excitatory neurons and inhibitory interneurons in the developing mammalian neocortex.
However, the developmental hierarchy of the hypothalamus represents a conservative but extremely diverse and complex brain structure, which is still poorly understood.
The hypothalamus maintains the homeostasis of animals by regulating endocrine, autonomy and behavioral functions.
These functions include hunger, sleep, thirst, circadian rhythm, body temperature, mood regulation, libido, and hormone release.
The functional complexity of the hypothalamus depends on the extreme neuronal diversity produced during brain development.
Hypothalamic neurons include large cell endocrine neurons (OXT [{[oxytocin], AVP [arginine vasopressin], etc.
), small cell secretory neurons (TRH [thyrotropin releasing hormone], CRH [adrenal stimulating hormone] Corticosteroid releasing hormone], etc.
), large peptidergic projection neurons (HCRT [hypocretin], MCH [melanin concentrating hormone], etc.
), small cell peptidergic neurons (POMC [proopiomelanocortin], AgRP [agouti related protein], etc.
), And other inhibitory or excitatory local loop neurons.
For a long time, various neuropeptides have been the basis for defining neuronal subtypes and understanding the function of the hypothalamus.
Contrary to a large number of studies that reveal the circuits and functions of different hypothalamic neurons, how to develop neuronal subtype-specific heterogeneity from the common radial glial cells (RGC) as embryonic neural stem cells (NSC) during development Little is known.
Two models have been proposed for the origin and process of neuronal diversity in mammalian brains.
One model proposes that cortical RGCs in turn produce fate-determining intermediate progenitor cells (IPC), which differentiate into deep and upper excitatory neurons.
Recent single-cell analysis further supports the theory that the diversity of cortical inhibitory interneurons has been predetermined at the progenitor cell level or shortly after mitosis.
It is worth noting that in the neocortex, the origin of excitatory glutamatergic and inhibitory GABAergic neurons and their direct progenitor cells are spatially separated and diverse.
The second model assumes that retinal progenitor cells randomly adopt multiple cell fates during the differentiation process.
Considering the profusion of molecularly diverse neurons and their key role in maintaining homeostatic control, it is important to study the developmental diversity and trajectories of hypothalamic neurons.
Here, the study sequenced the hypothalamic cells produced by the Rax lineage for single-cell RNA sequencing, and traced the developmental trajectories of RGC, IPC, newborn neurons, and peptidergic neurons in the neural lineage hierarchy.
Contrary to the predetermined fate model in the cortex and the random model in the retina, the combination of transcriptomics analysis and lineage tracking data supports a cascading diversification model in which RGC, IPC and newborn neurons promote the diversification of hypothalamic neuronal fate .
The study also identified the embryonic origins of postpartum monocytes and regulators of designated neuron subtypes, which further provides insight into hypothalamic plasticity and gains valuable insights into hypothalamic diseases such as anorexia, narcolepsy, and insomnia The development prospects.
Reference message:
However, its molecular development trajectory and the origin of neuronal diversity are still unclear.
On April 21, 2021, Qingfeng Wu's team from the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences published a research paper titled "Cascade diversification directs generation of neuronal diversity in the hypothalamus" in Cell Stem Cell online.
The research introduced the research paper from Rax + The transcriptome of 43261 cells in the hypothalamic neuroepithelium is used to map the development of mouse hypothalamus and the trajectory of firing glial cells (RGC), intermediate progenitor cells (IPC), newborn neurons and peptidergic neurons.
The study showed that RGCs adopt conservative strategies for pluripotent differentiation, but they generate Ascl1 + and Neurog2 + IPC.
Cloning analysis further proved that a single RGC can produce multiple neuronal subtypes.
Studies have shown that multiple cell types along the lineage hierarchy promote the diversification of the fate of hypothalamic neurons in a gradual manner, which suggests a cascading diversification model that deconstructs the origin of neuronal diversity.
In conclusion, the study also determined the embryonic origin of the regulators of postpartum monocytes and designated neuron subtypes, which further provides valuable insights into hypothalamic plasticity and gains in hypothalamic diseases such as anorexia, narcolepsy and insomnia.
Insights provide development prospects.In addition, on April 16, 2021, Wu Qingfeng and other teams from the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences published a research paper entitled "Hypothalamic Rax + tanycytes contribute to tissue repair and tumorigenesis upon oncogene activation in mice" in Nature Communications.
The study combined single-cell transcriptome sequencing, cell lineage tracking, single-molecule in situ hybridization and other technologies to reveal that most of the Rax-positive stretched cells in mouse ME are in a quiescent state, but quickly enter the cell cycle for self-renewal and regeneration after nerve injury .
Under mechanical injury conditions, tissue repair requires activation of the Igf1r signaling pathway in stretched cells.
In addition, the activation of Braf's proto-oncogene is sufficient to transform Rax-positive stretched cells into proliferating tumor cells, and eventually develop into papillary craniopharyngioma-like tumors.
Together, these findings reveal the regeneration and tumorigenic potential of stretched cells.
This study explored the characteristics of stretch cells in depth, which will help us manipulate the biological characteristics of stretch cells to regulate hypothalamic function, and explore the pathogenesis and diagnosis and treatment of clinically relevant tumors.
Understanding the mechanism of brain development requires a systematic investigation of neural progenitor cell types, their lineage specifications, and the development and maturation of neurons after mitosis.
Cumulative evidence based on single-cell transcriptomics analysis revealed the transcriptional heterogeneity of cortical neural progenitor cells, their temporal patterns, and the differentiation trajectory of excitatory neurons and inhibitory interneurons in the developing mammalian neocortex.
However, the developmental hierarchy of the hypothalamus represents a conservative but extremely diverse and complex brain structure, which is still poorly understood.
The hypothalamus maintains the homeostasis of animals by regulating endocrine, autonomy and behavioral functions.
These functions include hunger, sleep, thirst, circadian rhythm, body temperature, mood regulation, libido, and hormone release.
The functional complexity of the hypothalamus depends on the extreme neuronal diversity produced during brain development.
Hypothalamic neurons include large cell endocrine neurons (OXT [{[oxytocin], AVP [arginine vasopressin], etc.
), small cell secretory neurons (TRH [thyrotropin releasing hormone], CRH [adrenal stimulating hormone] Corticosteroid releasing hormone], etc.
), large peptidergic projection neurons (HCRT [hypocretin], MCH [melanin concentrating hormone], etc.
), small cell peptidergic neurons (POMC [proopiomelanocortin], AgRP [agouti related protein], etc.
), And other inhibitory or excitatory local loop neurons.
For a long time, various neuropeptides have been the basis for defining neuronal subtypes and understanding the function of the hypothalamus.
Contrary to a large number of studies that reveal the circuits and functions of different hypothalamic neurons, how to develop neuronal subtype-specific heterogeneity from the common radial glial cells (RGC) as embryonic neural stem cells (NSC) during development Little is known.
Two models have been proposed for the origin and process of neuronal diversity in mammalian brains.
One model proposes that cortical RGCs in turn produce fate-determining intermediate progenitor cells (IPC), which differentiate into deep and upper excitatory neurons.
Recent single-cell analysis further supports the theory that the diversity of cortical inhibitory interneurons has been predetermined at the progenitor cell level or shortly after mitosis.
It is worth noting that in the neocortex, the origin of excitatory glutamatergic and inhibitory GABAergic neurons and their direct progenitor cells are spatially separated and diverse.
The second model assumes that retinal progenitor cells randomly adopt multiple cell fates during the differentiation process.
Considering the profusion of molecularly diverse neurons and their key role in maintaining homeostatic control, it is important to study the developmental diversity and trajectories of hypothalamic neurons.
Here, the study sequenced the hypothalamic cells produced by the Rax lineage for single-cell RNA sequencing, and traced the developmental trajectories of RGC, IPC, newborn neurons, and peptidergic neurons in the neural lineage hierarchy.
Contrary to the predetermined fate model in the cortex and the random model in the retina, the combination of transcriptomics analysis and lineage tracking data supports a cascading diversification model in which RGC, IPC and newborn neurons promote the diversification of hypothalamic neuronal fate .
The study also identified the embryonic origins of postpartum monocytes and regulators of designated neuron subtypes, which further provides insight into hypothalamic plasticity and gains valuable insights into hypothalamic diseases such as anorexia, narcolepsy, and insomnia The development prospects.
Reference message:
