{"doi":"10.1038/s41540-019-0095-2","title":"Identification of an early cell fate regulator by detecting dynamics in transcriptional heterogeneity and co-regulation during astrocyte differentiation","abstract":"<jats:title>Abstract</jats:title><jats:p>There are an increasing number of reports that characterize the temporal behavior of gene expression at the single-cell level during cell differentiation. Despite accumulation of data describing the heterogeneity of biological responses, the dynamics of gene expression heterogeneity and its regulation during the differentiation process have not been studied systematically. To understand transcriptional heterogeneity during astrocyte differentiation, we analyzed single-cell transcriptional data from cells representing the different stages of astrocyte differentiation. When we compared the transcriptional variability of co-expressed genes between the undifferentiated and differentiated states, we found that there was significant increase in transcriptional variability in the undifferentiated state. The genes showing large changes in both “variability” and “correlation” between neural stem cells (NSCs) and astrocytes were found to be functionally involved in astrocyte differentiation. We determined that these genes are potentially regulated by <jats:italic>Ascl1</jats:italic>, a previously known oscillatory gene in NSCs. Pharmacological blockade of <jats:italic>Ntsr2</jats:italic>, which is transcriptionally co-regulated with <jats:italic>Ascl1</jats:italic>, showed that <jats:italic>Ntsr2</jats:italic> may play an important role in the differentiation from NSCs to astrocytes. This study shows the importance of characterizing transcriptional heterogeneity and rearrangement of the co-regulation network between different cell states. It also highlights the potential for identifying novel regulators of cell differentiation that will further increase our understanding of the molecular mechanisms underlying the differentiation process.</jats:p>","journal":"npj Systems Biology and Applications","year":2019,"id":627955,"datarank":0.38474240361923057,"base_score":2.5649493574615367,"endowment":2.5649493574615367,"self_citation_contribution":0.38474240361923057,"citation_network_contribution":0.0,"self_endowment_contribution":0.38474240361923057,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1625572,"name":"Ryuji Kato","orcid":null,"position":1,"is_corresponding":false},{"id":1625573,"name":"Hiroyuki Honda","orcid":null,"position":2,"is_corresponding":false},{"id":1625571,"name":"Tatsuya Ando","orcid":"0000-0003-2274-5807","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Identification of an early cell fate regulator by detecting dynamics in transcriptional heterogeneity and co-regulation during astrocyte differentiation","abstract":"<jats:title>Abstract</jats:title><jats:p>There are an increasing number of reports that characterize the temporal behavior of gene expression at the single-cell level during cell differentiation. Despite accumulation of data describing the heterogeneity of biological responses, the dynamics of gene expression heterogeneity and its regulation during the differentiation process have not been studied systematically. To understand transcriptional heterogeneity during astrocyte differentiation, we analyzed single-cell transcriptional data from cells representing the different stages of astrocyte differentiation. When we compared the transcriptional variability of co-expressed genes between the undifferentiated and differentiated states, we found that there was significant increase in transcriptional variability in the undifferentiated state. The genes showing large changes in both “variability” and “correlation” between neural stem cells (NSCs) and astrocytes were found to be functionally involved in astrocyte differentiation. We determined that these genes are potentially regulated by <jats:italic>Ascl1</jats:italic>, a previously known oscillatory gene in NSCs. Pharmacological blockade of <jats:italic>Ntsr2</jats:italic>, which is transcriptionally co-regulated with <jats:italic>Ascl1</jats:italic>, showed that <jats:italic>Ntsr2</jats:italic> may play an important role in the differentiation from NSCs to astrocytes. This study shows the importance of characterizing transcriptional heterogeneity and rearrangement of the co-regulation network between different cell states. It also highlights the potential for identifying novel regulators of cell differentiation that will further increase our understanding of the molecular mechanisms underlying the differentiation process.</jats:p>","is_dataset_classified":null,"base_score":2.5649493574615367,"endowment":2.5649493574615367,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"31098297","pmcid":"PMC6506553","openalex_id":"https://openalex.org/W2944052185","authors":[],"funders":[{"funder_name":"Japan Science and Technology Agency (JST) Program for Creating STart-ups from Advanced Research and Technology","grant_id":"","title":null}],"total_grants":1,"fwci":0.9103,"citation_percentile":0.726978,"influential_citations":0,"citation_trend":[{"year":2019,"count":1},{"year":2020,"count":1},{"year":2021,"count":5},{"year":2022,"count":5}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.nature.com/articles/s41540-019-0095-2.pdf","host_type":"journal"},{"url":"https://www.nature.com/articles/s41540-019-0095-2.pdf","host_type":"publisher"},{"url":"https://www.nature.com/articles/s41540-019-0095-2","host_type":"publisher"},{"url":"https://doi.org/10.1038/s41540-019-0095-2","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/31098297","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/6506553","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC6506553","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC6506553?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Gene Regulatory Network Analysis","Single-cell and spatial transcriptomics","Genetics, Aging, and Longevity in Model Organisms","Animals","Astrocytes","Cell Differentiation","Databases, Genetic","Gene Expression Profiling","Gene Expression Regulation, Developmental","Gene Regulatory Networks","Humans","Mice","Neural Stem Cells","Neurogenesis","Single-Cell Analysis"],"mesh_terms":["Animals","Astrocytes","Cell Differentiation","Humans","Gene Expression Regulation, Developmental","Gene Expression Profiling","Databases, Genetic","Mice","Gene Regulatory Networks","Neurogenesis","Neural Stem Cells","Single-Cell Analysis"],"keywords":["Biology","Cellular differentiation","Astrocyte","Transcriptional regulation","Neural stem cell","Regulation of gene expression","Cell fate determination","Gene expression","Cell type","Gene regulatory network","Cell","Gene","Cell biology","Stem cell","Genetics","Transcription factor","Neuroscience","Central nervous system","Stem Cells","Dynamical Systems","Dynamic Networks","Cellular Noise"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"gen"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-05T10:18:24.946458Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}