中国科学院遗传与发育生物学研究所

分子发育生物学国家重点实验室

中国科学院脑智卓越中心

RESEARCH

(1) Development of nuclear brain structure

Mammalian brain consists of both laminar (e.g. neocortex and retina) and nuclear (e.g. thalamus, hypothalamus and brain stem) structures, which directly affect behavior and cognition. Very little is known about spatial organizational principles of nuclear brain structures at single-cell level, in contrast to well-studied stratified neocortex. We are using single-cell analysis approach such as clonal analysis (single-cell lineage tracing), single-cell RNAseq and single-cell genetic deletion to investigate the behavior of embryonic neural stem cells; the generation, migration and connection of neurons in hypothalamus and brain stem; and the molecular and cellular mechanisms underlying congenital neural disease.

(2) Neural control of metabolic disorders

With the improvement of material living conditions, obesity has become a significant public health concern affecting more than half a billion people worldwide. Multiple hypothalamic nuclei and their associated neural circuits play an important role in regulating human feeding and body metabolism. On the one hand, we are identifying the novel neuronal ensemble involved in regulating feeding behavior and body metabolism. One the other hand, we are intrigued by the features and functions of  tanycytes, the putative hypothalamic stem cells.

 

More specifically, we are focusing on the role of adult neural stem cells (NSCs) in regulating aging and obesity as well as the potential mechanisms. Canonical adult NSCs reside in the subventricular zone (SVZ) lining lateral ventricle and the subgranular zone (SGZ) within hippocampus and decay during the aging process. Recently, it has been reported that adult hypothalamic NSCs regulate feeding behavior, metabolic disorders and systemic ageing. We will use lineage tracing approach to investigate the behavior of adult hypothalamic NSCs under distinct environmental context and its effect on organismal metabolism. Furthermore, we are also interested in the incorporation of hypothalamic new-born neurons in neural circuit.   

(3) Homeostatic regulation of neural stem cells

Homeostasis maintenance of neural stem cells is critical for neural development and neural injury regeneration. Dysregulation of embryonic NSC homeostasis cause neural developmental disorders, such as autism and intellectual disability. Disruption of adult NSC homeostasis may result in schizophrenia, mood disorder and progeria. We are using lineage tracing and genomic editing approaches to investigate the molecular mechanisms underlying homeostatic regulation of NSCs under physiological and pathological conditions.

1、大脑核团的发育

哺乳动物大脑包括层状结构(大脑皮层、视网膜等)和核团结构(丘脑、下丘脑、脑干等),这些神经元的组织结构将直接影响神经信息传递和认知行为。虽然层状结构大脑皮层的组织原则在过去十年里已经得到比较深入的研究,然而学界对核团类结构的空间构架原则所知甚少。我们将利用单细胞谱系追踪技术、单细胞测序、单细胞基因敲除等探索丘脑和下丘脑核团的干细胞起源,神经元多样性的起源,子代神经元的迁移方式和路线,神经元投射的方式,核团内细胞微环路的形成和核团形成的基本原则,以及先天性神经相关疾病的分子细胞机理。

2、神经调控代谢的机制

随着物质生活条件的改善,肥胖在全球范围内成为危害人体健康的重要疾病。下丘脑弓状核和室旁核神经元及其相关神经环路在调控人体摄食和机体代谢方面发挥着重要的作用。我们一方面关注下丘脑神经元群调控代谢的新机制;另一方面也探索下丘脑神经干细胞在各种环境下的稳态维持及其失调对机体代谢的影响,同时关注下丘脑新生神经元的环路整合。

3、神经干细胞的稳态调控

神经干细胞的稳态维持对于神经发育和损伤再生至关重要,胚胎期神经干细胞的稳态失调可以导致大脑发育异常,出现自闭症、智力障碍等疾病;成年期神经干细胞的稳态失调可以导致精神分裂症、情绪障碍、早衰等疾病。我们利用谱系追踪技术、基因编辑技术等研究调控神经干细胞稳态的分子机制,来研究中心体复合物对大脑发育的调控、分泌性因子对神经组织稳态的调节以及胶质瘤发生的机制、神经损伤状态下室管膜细胞重编程的方式和机制等。