RESEARCH
(1) Hypothalamus Development: From Neurogenesis to Circuit Assembly
Hypothalamus maintains systemic homeostasis by regulating endocrine, autonomic and behavioral functions, ranging from hunger, sleep, thirst, circadian rhythm and body temperature to mood regulation, sex drive and hormonal release. However, little is known about the hypothalamus development including its patterning, neurogenesis and circuit assembly across different vertebrate species. We combine sing-cell lineage tracing (i.e. clonal analysis), single-cell multi-omics and cross-species comparisons to systematically uncover principles of hypothalamic neurogenesis. We have proposed “cascade diversification model”, reconstructed hypothalamic lineages, and demonstrated hierarchical fate determination of hypothalamic neurons (Cell Stem Cell, 2021; Dev Cell, 2025; Sci Adv, 2022; PLoS Biol, 2018). Given the diverse neuronal diversity, complex neuronal connection and critical neuronal function in the hypothalamus, more efforts are required to decode the processes and mechanisms of neuronal generation and circuit assembly.
(2) Hypothalamic Control of Metabolism
The hypothalamus not only senses peripheral glucose and lipid signals but also secretes neurotransmitters, neuropeptides and neurohormones to coordinate interactions between the brain and peripheral organs (e.g. adipose tissue, gut, liver), thereby maintaining energy homeostasis. However, how the hypothalamus communicates with peripheral organs remains unclear. Our team has identified novel hypothalamic neuronal subtypes and revealed their circuit mechanisms in regulating energy expenditure (Neuron, 2022).
(3) Homeostatic Regulation of Neural Stem cells and Brain Tumors
Neural stem/progenitor cells (NSPCs) maintain a dynamic balance in quantity, activity, self-renewal and differentiation under physiological and pathological conditions, a phenomenon known as homeostasis. Homeostatic dysregulation of NSPCs causes neurodevelopmental disorders, such as autism, intellectual disability, macrocephaly and brain tumors. We discovered the presence of cell competition between NSPCs and its role in regulating brain size (Dev Cell, 2023; Natl Sci Rev, 2025; Cell Rep, 2020; Cell, 2012). We also identified hypothalamic NSPCs as the cellular origin of craniopharyngioma, allowing for animal modeling and drug screening of this tumor (Sci Transl Med, 2024; Nat Commun, 2021).
(1) 下丘脑发育：从神经发生到环路组装
下丘脑通过调节内分泌、自主神经和行为功能来维持机体内稳态，包括饥饿、睡眠、体温、口渴、昼夜节律、情绪调节、性欲和激素释放等。然而，对于不同脊椎动物的下丘脑发育，包括其模式生成、神经发生和环路组装，领域内所知甚少。我们团队结合单细胞谱系追踪（即克隆分析）、单细胞多组学和跨物种比较等方法，系统性揭示了下丘脑神经发生的规律，提出了“级联放大论”、“多谱系起源”和“阶梯式命运决定”等概念 (Cell Stem Cell, 2021; Dev Cell, 2025; Sci Adv, 2022; PLoS Bio, 2018)。由于下丘脑神经元连接的复杂性以和功能的重要性，我们需要付出更多的努力来解码神经元生成和环路组装的过程和机制。
(2) 下丘脑介导肥胖的神经体液机制
下丘脑不仅可以感知来自外周的糖脂信号，还能分泌神经递质、神经肽、神经激素等，用以协调大脑和外周器官（脂肪、肠道、肝脏）之间的相互协作，以维持机体的能量平衡。然而，下丘脑如何与外周代谢器官进行交互尚不清楚。我们团队鉴定出新型下丘脑神经元，并揭示其调控机体能量消耗的神经机制 (Neuron, 2025)。
(3) 神经干细胞的稳态调控与脑肿瘤
神经干细胞在数量、活性、自我更新与分化之间维持一种动态平衡，这种现象称为稳态。神经干细胞稳态对脑发育、脑结构和脑功能至关重要；其稳态失衡可导致自闭症、智力障碍、巨头症、脑肿瘤等疾病。我们团队研究生理与病理条件下神经干细胞稳态的调控机制，首次发现神经祖细胞竞争现象，及其对干细胞数量和脑器官大小的调控作用；首次揭示下丘脑干细胞失稳态可诱发颅咽管瘤，进而筛选出先导药物 (Dev Cell, 2023; Sci Transl Med, 2024; Nat Commun, 2021; Cell Rep, 2020; Cell, 2012)。