biostudies-literatureConrad CNIAID NIH HHSNHLBI NIH HHSMedical Research CouncilWellcome TrustNIH HHS1975-1986https://www.ebi.ac.uk/biostudies/studies/S-EPMC7617544biostudies-literatureUnknown145(18)<h4>Abstract</h4>Although the bone marrow is the main site of blood cell production in adults, rare pools of hematopoietic stem and progenitor cells have been found in extramedullary organs. In mice, we have previously shown that the lung contains hematopoietic progenitor cells and is a site of platelet production. Here, in the adult human lung, we show that functional hematopoietic precursors reside in the extravascular spaces with a frequency similar to the bone marrow and are capable of proliferation and engraftment in mice. The gene signature of pulmonary and medullary CD34+ hematopoietic progenitors indicates greater baseline activation of immune-, megakaryocyte/platelet-, and erythroid-related pathways in lung progenitors. Spatial transcriptomics mapped blood progenitors in the lung to an alveolar interstitium niche with only a few cells identified in an intravascular location. In human blood samples collected for stem cell transplantation, CD34+ cells with a lung signature enriched the mobilized pool of hematopoietic stem cells. These results identify the lung as a pool for uniquely programmed blood stem and progenitor cells with the potential to support hematopoiesis in humans.BloodDecoding functional hematopoietic progenitor cells in the adult human lung.PMC7617544107630R01 AI165919203151/A/16/Z203151/Z/16/Z203151R35 HL161241MC_PC_17230S10 OD028511Wismer HMagnen MNaser MCleary SJLeavitt ADCombes AJLooney MRDe Giovanni MQiu LMende NVenkataramani UPassegue ESamad BLaurenti EConrad CTsui JTian JJfalseDecoding functional hematopoietic progenitor cells in the adult human lung.<h4>Abstract</h4>Although the bone marrow is the main site of blood cell production in adults, rare pools of hematopoietic stem and progenitor cells have been found in extramedullary organs. In mice, we have previously shown that the lung contains hematopoietic progenitor cells and is a site of platelet production. Here, in the adult human lung, we show that functional hematopoietic precursors reside in the extravascular spaces with a frequency similar to the bone marrow and are capable of proliferation and engraftment in mice. The gene signature of pulmonary and medullary CD34+ hematopoietic progenitors indicates greater baseline activation of immune-, megakaryocyte/platelet-, and erythroid-related pathways in lung progenitors. Spatial transcriptomics mapped blood progenitors in the lung to an alveolar interstitium niche with only a few cells identified in an intravascular location. In human blood samples collected for stem cell transplantation, CD34+ cells with a lung signature enriched the mobilized pool of hematopoietic stem cells. These results identify the lung as a pool for uniquely programmed blood stem and progenitor cells with the potential to support hematopoiesis in humans.2025-01-01T00:00:00Z2025 May2026-06-02T21:05:45.964Z2025-07-06T03:05:52.917ZS-EPMC76175444001479710.1182/blood.2024027884