{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:03:01Z","timestamp":1790208181387,"version":"4.1.0"},"reference-count":64,"publisher":"American Society of Hematology","issue":"19","license":[{"start":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T00:00:00Z","timestamp":1709683200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,5,9]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>In physiological conditions, few circulating hematopoietic stem\/progenitor cells (cHSPCs) are present in the peripheral blood, but their contribution to human hematopoiesis remain unsolved. By integrating advanced immunophenotyping, single-cell transcriptional and functional profiling, and integration site (IS) clonal tracking, we unveiled the biological properties and the transcriptional features of human cHSPC subpopulations in relationship to their bone marrow (BM) counterpart. We found that cHSPCs reduced in cell count over aging and are enriched for primitive, lymphoid, and erythroid subpopulations, showing preactivated transcriptional and functional state. Moreover, cHSPCs\u00a0have low expression of multiple BM-retention molecules but maintain their homing potential after xenotransplantation. By generating a comprehensive human organ-resident HSPC data\u00a0set based on\u00a0single-cell RNA sequencing data, we detected organ-specific seeding properties of the distinct trafficking HSPC subpopulations. Notably, circulating multi-lymphoid progenitors are primed for seeding the thymus and actively contribute to T-cell production. Human clonal tracking data from patients receiving gene therapy (GT) also showed that cHSPCs\u00a0connect distant BM niches and participate in\u00a0steady-state hematopoietic production, with primitive cHSPCs\u00a0having the highest recirculation capability to travel in and out of the BM. Finally, in case of hematopoietic impairment, cHSPCs\u00a0composition reflects the BM-HSPC content and might represent a biomarker of the BM state for clinical and research purposes. Overall, our comprehensive work unveiled fundamental insights into the\u00a0in\u00a0vivo\u00a0dynamics of human HSPC trafficking and its role in sustaining hematopoietic homeostasis. GT patients\u2019 clinical trials were registered at\u00a0ClinicalTrials.gov\u00a0(NCT01515462 and NCT03837483) and EudraCT (2009-017346-32 and 2018-003842-18).<\/jats:p><\/jats:sec>","DOI":"10.1182\/blood.2023022666","type":"journal-article","created":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T16:55:23Z","timestamp":1709744123000},"page":"1937-1952","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":28,"title":["Circulating hematopoietic stem\/progenitor cell subsets\u00a0contribute to human hematopoietic homeostasis"],"prefix":"10.1182","volume":"143","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-2988-5387","authenticated-orcid":false,"given":"Pamela","family":"Quaranta","sequence":"first","affiliation":[{"name":"1San Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, Milan, Italy"},{"name":"2Universit\u00e0 Vita-Salute San Raffaele, Milan, 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