Decoding functional hematopoietic progenitor cells in the adult human lung

Area of Science:

• Hematology
• Pulmonary Medicine
• Stem Cell Biology

Background:

• Bone marrow is the primary site of adult hematopoiesis.
• Extramedullary hematopoietic stem and progenitor cells (HSPCs) exist in rare pools.
• Previous studies identified mouse lung HSPCs and platelet production.

Purpose of the Study:

• To investigate the presence and function of hematopoietic precursors in the adult human lung.
• To characterize the gene expression and localization of lung-resident blood progenitors.
• To assess the potential of pulmonary HSPCs in supporting hematopoiesis.

Main Methods:

• Analysis of human lung tissue for hematopoietic precursors.
• Flow cytometry and functional assays for cell proliferation and engraftment in mice.
• Gene expression profiling (transcriptomics) of pulmonary and bone marrow CD34+ cells.
• Spatial transcriptomics to map progenitor cell location within the lung.

Main Results:

• Functional hematopoietic precursors were found in adult human lung extravascular spaces at frequencies comparable to bone marrow.
• Pulmonary CD34+ progenitors exhibited greater baseline activation of immune, megakaryocyte/platelet, and erythroid pathways compared to bone marrow progenitors.
• Spatial transcriptomics revealed lung blood progenitors primarily in the alveolar interstitium.
• Human CD34+ cells with a lung signature were found to enrich the mobilized hematopoietic stem cell pool.

Conclusions:

• The adult human lung harbors a significant pool of uniquely programmed blood stem and progenitor cells.
• These pulmonary progenitors possess functional capabilities, including proliferation and engraftment potential.
• The lung represents a potential source of cells that can support human hematopoiesis.