{"doi":"10.1093/stmcls/sxad022","title":"Dynamics of Chromatin Accessibility During Hematopoietic Stem Cell Differentiation Into Progressively Lineage-Committed Progeny","abstract":"Epigenetic mechanisms regulate the multilineage differentiation capacity of hematopoietic stem cells (HSCs) into a variety of blood and immune cells. Mapping the chromatin dynamics of functionally defined cell populations will shed mechanistic insight into 2 major, unanswered questions in stem cell biology: how does epigenetic identity contribute to a cell type's lineage potential, and how do cascades of chromatin remodeling dictate ensuing fate decisions? Our recent work revealed evidence of multilineage gene priming in HSCs, where open cis-regulatory elements (CREs) exclusively shared between HSCs and unipotent lineage cells were enriched for DNA binding motifs of known lineage-specific transcription factors. Oligopotent progenitor populations operating between the HSCs and unipotent cells play essential roles in effecting hematopoietic homeostasis. To test the hypothesis that selective HSC-primed lineage-specific CREs remain accessible throughout differentiation, we used ATAC-seq to map the temporal dynamics of chromatin remodeling during progenitor differentiation. We observed epigenetic-driven clustering of oligopotent and unipotent progenitors into distinct erythromyeloid and lymphoid branches, with multipotent HSCs and MPPs associating with the erythromyeloid lineage. We mapped the dynamics of lineage-primed CREs throughout hematopoiesis and identified both unique and shared CREs as potential lineage reinforcement mechanisms at fate branch points. Additionally, quantification of genome-wide peak count and size revealed overall greater chromatin accessibility in HSCs, allowing us to identify HSC-unique peaks as putative regulators of self-renewal and multilineage potential. Finally, CRISPRi-mediated targeting of ATACseq-identified putative CREs in HSCs allowed us to demonstrate the functional role of selective CREs in lineage-specific gene expression. These findings provide insight into the regulation of stem cell multipotency and lineage commitment throughout hematopoiesis and serve as a resource to test functional drivers of hematopoietic lineage fate.","journal":"Stem Cells","year":2023,"id":328578,"datarank":0.47670807455219194,"base_score":3.1780538303479458,"endowment":3.1780538303479458,"self_citation_contribution":0.47670807455219194,"citation_network_contribution":0.0,"self_endowment_contribution":0.47670807455219194,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":23,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9459,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":685364,"name":"Alessandra Rodriguez y Baena","orcid":"0000-0003-2510-7173","position":1,"is_corresponding":false},{"id":560748,"name":"Roman E. Reggiardo","orcid":"0000-0001-6309-249X","position":2,"is_corresponding":false},{"id":351421,"name":"Atesh Worthington","orcid":"0000-0003-3676-8735","position":3,"is_corresponding":false},{"id":1050482,"name":"Connor S Mattingly","orcid":null,"position":4,"is_corresponding":false},{"id":492138,"name":"Donna Poscablo","orcid":"0000-0002-5781-7121","position":5,"is_corresponding":false},{"id":560747,"name":"Jana Krietsch","orcid":"0000-0001-6533-3058","position":6,"is_corresponding":false},{"id":81155,"name":"Michael T. McManus","orcid":"0000-0003-3013-6569","position":7,"is_corresponding":false},{"id":237816,"name":"Susan Carpenter","orcid":"0000-0002-5600-5404","position":8,"is_corresponding":false},{"id":560749,"name":"Daniel H. Kim","orcid":"0000-0003-0684-6245","position":9,"is_corresponding":false},{"id":492139,"name":"E. Camilla Forsberg","orcid":"0000-0002-8740-4299","position":10,"is_corresponding":false},{"id":560746,"name":"Eric W. Martin","orcid":"0000-0003-0020-0187","position":0,"is_corresponding":true}],"reference_count":89,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:08:52.196069Z","pmid":"36945732","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":[]}