Transcription factors governing the development of GHRH-neurons

控制 GHRH 神经元发育的转录因子

基本信息

批准号：
10201931
负责人：
JAE W LEE
金额：
$ 55.83万
依托单位：
STATE UNIVERSITY OF NEW YORK AT BUFFALO
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-15 至 2021-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10201931
关键词：
Area Binding Biochemical Cells ChIP-seq Data Data Set Development Developmental Gene Dwarfism Embryo Embryonic Development Ensure FOXP2 gene Genes Goals Growth Growth and Development function Homeostasis Hypothalamic structure Immunohistochemistry In Situ Hybridization Individual Knockout Mice Life Link Maps Metabolic Diseases Methods Molecular Mus Neurons Pathway interactions Pattern Physiological Play Process Production Regulation Regulator Genes Regulatory Pathway Reporting Reproduction Research Research Project Summaries Role Somatotropin-Releasing Hormone Structure of nucleus infundibularis hypothalami Testing Time Work cell type chromatin immunoprecipitation conditional knockout energy balance experimental study feeding fight against genome-wide genome-wide analysis improved in vivo innovation mouse genetics mouse genome mouse model neuron development novel postnatal progenitor programs single-cell RNA sequencing transcription factor transcriptome

项目摘要

Project Summary The research goal of Lee lab is to decipher the gene regulatory network that directs the embryonic development of various types of neurons in the mouse arcuate nucleus of the hypothalamus (ARC). Neurons in the ARC centrally regulate various homeostatic processes critical for survival and reproduction. Despite extensive studies on the physiological roles of ARC neurons, the gene regulatory programs for their development are poorly understood. Lee lab has been pioneering this challenging area of studies by successfully combining mouse genetics and genome-wide studies. In particular, Lee lab accomplished the first ChIP-Seq (for chromatin immunoprecipitation followed by sequencing) and scRNA-Seq (for single cell RNA-Seq) analyses with developing ARC. Interestingly, many ARC neurons share common developmental lineages. This is likely to be critical to ensure the balanced production of different ARC neurons during embryogenesis, enabling a highly coordinated regulation of various homeostatic processes in later postnatal life, such as integration of feeding, reproduction, and growth. By performing scRNA-Seq with E15 ARC, when ARC neurons actively develop, Le lab identified transcription factors that are highly likely to play critical roles in the development of ARC neurons. These include the TFs Dlx1/2 and Prox1, which are hypothesized to play vital roles in establishing GHRH- neuronal fate over other related ARC neuronal lineages. By testing this hypothesis using an ensemble of biochemical and cellular methods, mouse genetics and genome-wide approaches, Lee lab wishes to advance the understanding of how common progenitors are guided to take a specific linage over other related ARC neuronal fates, resulting in the balanced development of various ARC neuronal types during embryogenesis.

项目摘要 Lee Lab的研究目标是破译指导胚胎开发的基因调节网络下丘脑（ARC）的小鼠弧形核中各种类型的神经元。弧中的神经元中央调节各种对生存和繁殖至关重要的稳态过程。尽管进行了广泛的研究关于电弧神经元的生理作用，其发展的基因调节程序很差理解。 Lee Lab通过成功将鼠标合并来开创这一具有挑战性的研究领域遗传学和全基因组研究。特别是，Lee Lab完成了第一个ChIP-Seq（染色质免疫沉淀，然后进行测序）和SCRNA-SEQ（用于单细胞RNA-Seq）分析开发弧。有趣的是，许多弧神经元具有共同的发育谱系。这可能是至关重要的是确保胚胎发生过程中不同弧神经元的平衡产生，从而能够高度在后来生活中对各种体内稳态过程的协调调节，例如喂养的整合，繁殖和增长。通过用E15 ARC进行SCRNA-SEQ，当弧神经元积极发展时，LE LAB确定了很可能在弧神经元发展中起关键作用的转录因子。其中包括TFS DLX1/2和Prox1，它们在建立GHRH-中起着至关重要的作用其他相关弧神经元谱系上的神经元命运。通过使用合奏的合奏来检验该假设 Lee Lab希望推进生化和细胞方法，小鼠遗传学和全基因组方法了解如何指导共同祖细胞在其他相关弧线上采用特定的线条神经元的命运，导致胚胎发生过程中各种弧神经元类型的平衡发展。