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The role of epigenetic modifiers in regulating the developmental plasticity of cranial neural crest cells

表观遗传修饰剂在调节颅神经嵴细胞发育可塑性中的作用

基本信息

批准号：
10211467
负责人：
Kristin Artinger
金额：
$ 22.77万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-01 至 2023-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10211467
关键词：
ATAC-seq Binding Sites Cartilage Cell Differentiation process Cell Lineage Cells Cephalic Chondrocytes Chromatin Chromatin Remodeling Factor Competence Congenital Abnormality DNA Binding Development Developmental Biology Differentiated Gene EVI1 gene Embryo Epigenetic Process Etiology Exhibits Gene Expression Genes Genetic Genetic Transcription Genomics Goals Growth Human Knowledge Link Mission Molecular Nature Neural Crest Neural Crest Cell Neuroglia Neuronal Differentiation Neurons Peripheral Nervous System Protein Family Proteins Public Health Regenerative Medicine Regulation Regulator Genes Research Role Series Signal Transduction Site System Testing Time Tissues Transcriptional Regulation Trigeminal System United States National Institutes of Health XCL1 gene Zebrafish bone cartilage cell cell type chromatin modification craniofacial craniofacial tissue developmental plasticity disability histone methyltransferase histone modification insight loss of function migration morphogens multipotent cell mutant neuromechanism progenitor recruit repaired single cell sequencing single-cell RNA sequencing stem stem cells tissue repair transcription factor transcriptome transcriptome sequencing

项目摘要

Summary How stem progenitor cells maintain plasticity for proper cell fate determination over developmental time is a fundamental question in developmental biology and regenerative medicine. Cranial neural crest cells (cNCCs) are an excellent example of a well defined cellular lineage transition in which multipotent cells step through a series of more restricted progenitors to give rise to diverse array of differentiated cell types, including neurons and glia of the peripheral nervous system as well as craniofacial cartilage and bone. Thus, understanding the genetic and epigenetic regulators in cNCC development is key to understanding how cell fate is determined as well as how cells can be reprogrammed. We hypothesize that the cNCC cartilage/neuron/glial progenitor retains plasticity through developmental time and cNCC fate acquisition is controlled by regulation of chromatin accessibility by prdm3. The rationale for the proposed studies is that an in-depth understanding of the specific factors involved in cNCC lineage transitions will provide insights into both normal developmental plasticity of cNCCs as well as how progenitors can be reprogramed for tissue repair. We will test this hypothesis in the following specific aims: 1) Test the hypothesis that prdm3 acts as a molecular cell fate switch during cNCC differentiation. Here we will test the hypothesis that prdm3 activity is required in cNCCs cell autonomously to promote the temporal recruitment of progenitors to cartilage by repressing neuronal cell fate. 2) Test the hypothesis that the cartilage/neuronal/glial (CNG) progenitor retains plasticity through developmental time and can be reprogramed by loss of prdm3. In Aim 2, hypothesis that CNG progenitors retain plasticity over developmental time and into larval stages and are reprogramed with loss of prdm3. 3) Test the hypothesis that Prdm3 regulates the timing of cNCC differentiation by controlling of genomic accessibility. In Aim 3, we will test the hypothesis that loss of Prdm3 leads to global alterations in chromatin state at cNCC progenitor genes, which in turn controls the timing of differentiation. Together, these studies will reveal basic information of how cNCCs differentiate into specific cell types during development. The results of this proposal have the potential to reveal important new insights into normal developmental plasticity of cNCCs such that tissue reprograming can be developed for the repair of damaged craniofacial tissues.

总结