{"doi":"10.1083/jcb.202010118","title":"Membrane-bound SCF and VCAM-1 synergistically regulate the morphology of hematopoietic stem cells","abstract":"Membrane-bound factors expressed by niche stromal cells constitute a unique class of localized cues and regulate the long-term functions of adult stem cells, yet little is known about the underlying mechanisms. Here, we used a supported lipid bilayer (SLB) to recapitulate the membrane-bound interactions between hematopoietic stem cells (HSCs) and niche stromal cells. HSCs cluster membrane-bound stem cell factor (mSCF) at the HSC-SLB interface. They further form a polarized morphology with aggregated mSCF under a large protrusion through a synergy with VCAM-1 on the bilayer, which drastically enhances HSC adhesion. These features are unique to mSCF and HSCs among the factors and hematopoietic populations we examined. The mSCF-VCAM-1 synergy and the polarized HSC morphology require PI3K signaling and cytoskeletal reorganization. The synergy also enhances nuclear retention of FOXO3a, a crucial factor for HSC maintenance, and minimizes its loss induced by soluble SCF. Our work thus reveals a unique role and signaling mechanism of membrane-bound factors in regulating stem cell morphology and function.","journal":"The Journal of Cell Biology","year":2021,"id":186743,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":20,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9511,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":422326,"name":"Hao Zhou","orcid":"0000-0002-3030-4270","position":1,"is_corresponding":false},{"id":745564,"name":"Kristen Nemes","orcid":null,"position":2,"is_corresponding":false},{"id":745059,"name":"Daniel Yen","orcid":"0000-0003-4101-9448","position":3,"is_corresponding":false},{"id":714888,"name":"Winfield Zhao","orcid":null,"position":4,"is_corresponding":false},{"id":697008,"name":"Charles Bramlett","orcid":"0000-0001-8663-1564","position":5,"is_corresponding":false},{"id":465509,"name":"Bowen Wang","orcid":"0000-0002-2974-9790","position":6,"is_corresponding":false},{"id":422330,"name":"Rong Lu","orcid":"0000-0002-5151-9246","position":7,"is_corresponding":false},{"id":337581,"name":"K. Robert Shen","orcid":"0000-0001-9605-1635","position":8,"is_corresponding":false},{"id":745058,"name":"Jia Hao","orcid":"0000-0002-6763-795X","position":0,"is_corresponding":true}],"reference_count":86,"raw_metadata":null,"created_at":"2026-07-18T23:48:46.850806Z","pmid":"34402812","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":[]}