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 blood cell production.
• Extramedullary hematopoietic stem and progenitor cells (HSPCs) are found in rare pools.
• Recent studies suggest the lung may be a site for blood production in mice.

Approach:

• Investigated functional hematopoietic precursors in the extravascular spaces of human lungs.
• Analyzed organ-specific gene signatures of pulmonary and medullary CD34+ hematopoietic progenitors.
• Utilized spatial transcriptomics to map blood progenitors within the lung's alveolar interstitium.

Key Points:

• Functional hematopoietic precursors reside in the human lung at frequencies comparable to bone marrow.
• Pulmonary HSPCs exhibit greater baseline activation of immune, megakaryocyte/platelet, and erythroid pathways.
• Spatial transcriptomics identified a vascular-rich alveolar interstitium as a niche for lung blood progenitors.
• Lung progenitors demonstrate proliferation and engraftment capabilities.

Conclusions:

• The human lung harbors a significant pool of uniquely programmed blood stem and progenitor cells.
• These pulmonary hematopoietic cells have the potential to contribute to human hematopoiesis.
• Identifies the lung as a novel extramedullary site for hematopoiesis in humans.