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The lung is a site of platelet biogenesis and a reservoir for haematopoietic progenitors

Abstract

Platelets are critical for haemostasis, thrombosis, and inflammatory responses1,2, but the events that lead to mature platelet production remain incompletely understood3. The bone marrow has been proposed to be a major site of platelet production, although there is indirect evidence that the lungs might also contribute to platelet biogenesis4,5,6,7. Here, by directly imaging the lung microcirculation in mice8, we show that a large number of megakaryocytes circulate through the lungs, where they dynamically release platelets. Megakaryocytes that release platelets in the lungs originate from extrapulmonary sites such as the bone marrow; we observed large megakaryocytes migrating out of the bone marrow space. The contribution of the lungs to platelet biogenesis is substantial, accounting for approximately 50% of total platelet production or 10 million platelets per hour. Furthermore, we identified populations of mature and immature megakaryocytes along with haematopoietic progenitors in the extravascular spaces of the lungs. Under conditions of thrombocytopenia and relative stem cell deficiency in the bone marrow9, these progenitors can migrate out of the lungs, repopulate the bone marrow, completely reconstitute blood platelet counts, and contribute to multiple haematopoietic lineages. These results identify the lungs as a primary site of terminal platelet production and an organ with considerable haematopoietic potential.

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Figure 1: The lungs are an important site of megakaryocyte circulation and platelet production.
Figure 2: Resident megakaryocytes are present in the extravascular spaces of the lung.
Figure 3: Lung-derived progenitors reconstitute platelet counts and haematopoietic stem cell deficiency in thrombocytopenic mice.
Figure 4: The lung contains haematopoietic progenitors, including megakaryocyte progenitors.

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References

  1. Semple, J. W ., Italiano, J. E., Jr & Freedman, J. Platelets and the immune continuum. Nat. Rev. Immunol. 11, 264–274 (2011)

    CAS  Article  Google Scholar 

  2. Versteeg, H. H., Heemskerk, J. W., Levi, M. & Reitsma, P. H. New fundamentals in hemostasis. Physiol. Rev. 93, 327–358 (2013)

    CAS  Article  Google Scholar 

  3. Machlus, K. R. & Italiano, J. E. Jr. The incredible journey: from megakaryocyte development to platelet formation. J. Cell Biol. 201, 785–796 (2013)

    CAS  Article  Google Scholar 

  4. Howell, W. H. & Donahue, D. D. The production of blood platelets in the lungs. J. Exp. Med. 65, 177–203 (1937)

    CAS  Article  Google Scholar 

  5. Levine, R. F. et al. Circulating megakaryocytes: delivery of large numbers of intact, mature megakaryocytes to the lungs. Eur. J. Haematol. 51, 233–246 (1993)

    CAS  Article  Google Scholar 

  6. Zucker-Franklin, D. & Philipp, C. S. Platelet production in the pulmonary capillary bed: new ultrastructural evidence for an old concept. Am. J. Pathol. 157, 69–74 (2000)

    CAS  Article  Google Scholar 

  7. Weyrich, A. S. & Zimmerman, G. A. Platelets in lung biology. Annu. Rev. Physiol. 75, 569–591 (2013)

    CAS  Article  Google Scholar 

  8. Looney, M. R. et al. Stabilized imaging of immune surveillance in the mouse lung. Nat. Methods 8, 91–96 (2011)

    CAS  Article  Google Scholar 

  9. Alexander, W. S., Roberts, A. W., Nicola, N. A., Li, R. & Metcalf, D. Deficiencies in progenitor cells of multiple hematopoietic lineages and defective megakaryocytopoiesis in mice lacking the thrombopoietic receptor c-Mpl. Blood 87, 2162–2170 (1996)

    CAS  PubMed  Google Scholar 

  10. Aschoff, L. Uber capillare Embolie von riesenkemhaltigen Zellen. Arch Pathol Anat Phys 134, 11–14 (1893)

    Article  Google Scholar 

  11. Kallinikos-Maniatis, A. Megakaryocytes and platelets in central venous and arterial blood. Acta Haematol. 42, 330–335 (1969)

    CAS  Article  Google Scholar 

  12. Tiedt, R., Schomber, T., Hao-Shen, H. & Skoda, R. C. Pf4-Cre transgenic mice allow the generation of lineage-restricted gene knockouts for studying megakaryocyte and platelet function in vivo. Blood 109, 1503–1506 (2007)

    CAS  Article  Google Scholar 

  13. Patel, S. R., Hartwig, J. H. & Italiano, J. E., Jr. The biogenesis of platelets from megakaryocyte proplatelets. J. Clin. Invest. 115, 3348–3354 (2005)

    CAS  Article  Google Scholar 

  14. Thon, J. N. et al. Cytoskeletal mechanics of proplatelet maturation and platelet release. J. Cell Biol. 191, 861–874 (2010)

    CAS  Article  Google Scholar 

  15. Trowbridge, E. A. et al. The origin of platelet count and volume. Clin. Phys. Physiol. Meas. 5, 145–170 (1984)

    CAS  Article  Google Scholar 

  16. Fuentes, R. et al. Infusion of mature megakaryocytes into mice yields functional platelets. J. Clin. Invest. 120, 3917–3922 (2010)

    CAS  Article  Google Scholar 

  17. Kaufman, R. M., Airo, R., Pollack, S. & Crosby, W. H. Circulating megakaryocytes and platelet release in the lung. Blood 26, 720–731 (1965)

    CAS  PubMed  Google Scholar 

  18. Sayah, D. M. et al. Neutrophil extracellular traps are pathogenic in primary graft dysfunction after lung transplantation. Am. J. Respir. Crit. Care Med. 191, 455–463 (2015)

    Article  Google Scholar 

  19. Junt, T. et al. Dynamic visualization of thrombopoiesis within bone marrow. Science 317, 1767–1770 (2007)

    ADS  CAS  Article  Google Scholar 

  20. Pereira, J. P., An, J., Xu, Y., Huang, Y. & Cyster, J. G. Cannabinoid receptor 2 mediates the retention of immature B cells in bone marrow sinusoids. Nat. Immunol. 10, 403–411 (2009)

    CAS  Article  Google Scholar 

  21. Liu, Z. J. et al. Expansion of the neonatal platelet mass is achieved via an extension of platelet lifespan. Blood 123, 3381–3389 (2014)

    CAS  Article  Google Scholar 

  22. Pronk, C. J. et al. Elucidation of the phenotypic, functional, and molecular topography of a myeloerythroid progenitor cell hierarchy. Cell Stem Cell 1, 428–442 (2007)

    CAS  Article  Google Scholar 

  23. Pietras, E. M. et al. Functionally distinct subsets of lineage-biased multipotent progenitors control blood production in normal and regenerative conditions. Cell Stem Cell 17, 35–46 (2015)

    CAS  Article  Google Scholar 

  24. Dunois-Lardé, C. et al. Exposure of human megakaryocytes to high shear rates accelerates platelet production. Blood 114, 1875–1883 (2009)

    Article  Google Scholar 

  25. Yamamoto, K., de Waard, V., Fearns, C. & Loskutoff, D. J. Tissue distribution and regulation of murine von Willebrand factor gene expression in vivo. Blood 92, 2791–2801 (1998)

    CAS  PubMed  Google Scholar 

  26. Haas, S. et al. Inflammation-induced emergency megakaryopoiesis driven by hematopoietic stem cell-like megakaryocyte progenitors. Cell Stem Cell 17, 422–434 (2015)

    CAS  Article  Google Scholar 

  27. Headley, M. B. et al. Visualization of immediate immune responses to pioneer metastatic cells in the lung. Nature 531, 513–517 (2016)

    ADS  CAS  Article  Google Scholar 

  28. Ortiz-Muñoz, G. et al. Aspirin-triggered 15-epi-lipoxin A4 regulates neutrophil-platelet aggregation and attenuates acute lung injury in mice. Blood 124, 2625–2634 (2014)

    Article  Google Scholar 

  29. Canals, M., Olivares, R. & Rosenmann, M. A radiographic method to estimate lung volume and its use in small mammals. Biol. Res. 38, 41–47 (2005)

    Article  Google Scholar 

  30. Cornelissen, I . et al. Roles and interactions among protease-activated receptors and P2ry12 in hemostasis and thrombosis. Proc. Natl Acad. Sci. USA 107, 18605–18610 (2010)

    ADS  CAS  Article  Google Scholar 

Download references

Acknowledgements

We thank the UCSF BIDC for assistance with 2PIVM and 3D printing; A. Hérault, E. Verovskaya and S. Y. Zhang from the Passegué laboratory for assistance with hematopoietic progenitor isolation and transplantation; and D. Erle and the UCSF SABRE Functional Genomics Facility for assistance with the RNA-sequencing experiments. This work was supported in part by NIH grants HL092471 to E.P., HL107386 and HL130324 to M.R.L., the UCSF Nina Ireland Program in Lung Health (M.R.L.), and the UCSF Program for Breakthrough Biomedical Research (M.R.L.).

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Authors and Affiliations

Authors

Contributions

E.L. designed and conducted most of the experiments, analysed the data, and wrote the manuscript. G.O.-M. designed and conducted experiments and analysed the data. A.C. and B.M. conducted experiments and analysed data. F.L. performed the lung transplantation experiments. D.M.S., E.E.T., M.B.H. and T.D. assisted in designing and conducting experiments. S.R.C, M.F.K. and A.D.L. assisted in designing experiments and provided editorial support on the manuscript. E.P. assisted in designing experiments, provided technical expertise with haematopoietic progenitor analyses, and provided editorial support on the manuscript. M.R.L. designed the experiments, conducted experiments, analysed data, and wrote the manuscript.

Corresponding author

Correspondence to Mark R. Looney.

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The authors declare no competing financial interests.

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Reviewer Information Nature thanks F. Ginhoux, S. Morrison, G. Zimmerman and the other anonymous reviewer(s) for their contribution to the peer review of this work.

Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Extended data figures and tables

Extended Data Figure 1 Megakaryocytes and proplatelets observed in lung circulation are from an extrapulmonary source.

a, Lung 2PIVM of a PF4-nTnG mouse (nuclear GFP). The presence of the mobile GFP+ nucleated cells (circled) indicates the presence of a nucleus in circulating megakaryocytes. b, Platelet counts in the blood before and after imaging. n.s., not significant (n = 3). c, Experimental schema of transplantation of lungs from mTmG mouse (perfused donor lung) to PF4-mTmG (recipient) mouse and vice-versa followed by 2PIVM. d, 2PIVM of a mTmG mouse lung showing no GFP signal. e, 2PIVM of an mTmG mouse lung transplanted into a PF4-mTmG recipient mouse showing GFP+ cells from recipient and platelet production in the lung. f, Bone marrow 2PIVM apparatus. g, Representative image of proplatelet release in bone marrow (BM) sinusoids (arrows). h, 2PIVM of PF4-mTmG mouse liver. Small platelets (GFP, green) were seen in the circulation but neither resident nor circulating megakaryocytes or proplatelets were observed. i, 2PIVM of PF4-mTmG mouse spleen. Sequential images show resident megakaryocytes (GFP, green) releasing proplatelets (arrows) in the spleen vasculature (in red).

Source data

Extended Data Figure 2 Resident megakaryocytes in the lungs and other organs.

a, Survey of PF4-tomato mouse lung visualized by 2PIVM. PF4-tomato-expressing cells (red) are found in high numbers in the lungs. Lung vasculature is labelled by intravascular injection of FITC dextran (green). A total area of 2.49 mm2 (1.6 mm × 1.6 mm) was imaged. b, Resident (static) GFP+ cells are found in a PF4-mTmG lungtransplanted into an mTmG mouse. c, d, 2PIVM images of bone marrow (c) and spleen (d) from PF4-mTmG mice. Many large megakaryocytes (GFP, green) are found in the bone marrow and spleen. e, Size characterization of resident (static) GFP+ cells by image analysis of PF4-mTmG lungs (n = 16), bone marrow (n = 12), and spleen (n = 16). Minimum-to-maximum boxplots are shown: the line in the middle of the box is plotted at the median, the box extends from the 25th to 75th percentiles and the whiskers range from the smallest to the largest values. The + indicates the mean.

Source data

Extended Data Figure 3 Surface expression of lung megakaryocytes compared to bone marrow megakaryocytes.

a, Flow cytometric analysis of nGFP+ cells from PF4-nTnG lungs. b, CD41 expression defines two populations of megakaryocytes: CD41+ (red) and CD41 (green). c, Positive surface expression of GPVI, c-Mpl and CD45 was detected in both populations. Unstained cells are plotted in blue. d, Surface expression of F4/80, CD34, CD11b, Sca-1 and c-Kit was not detected. ei, The CD41+ population has a higher percentage of CD61+ cells (e), CD42b+ cells (f) and larger cells (g) and had higher DNA content (h), as summarized in i (n = 3). j, Flow cytometric analysis of nGFP+ cells from PF4-nTnG bone marrow. km, Compared to the lungs, the bone marrow nGFP+ population has a higher percentage of CD41+ cells (n = 21–23) (k), CD61+ cells (n = 3) (l), and CD42b+ cells (n = 3) (m). Data are representative of three or more replicates. Mean ± s.d. are presented. Unpaired t-test: *P < 0.05, **P < 0.01, ***P < 0.001.

Source data

Extended Data Figure 4 Gene expression analysis of lung versus bone marrow megakaryocytes and bacterial pneumonia experiment reveal an immature profile and a potential role in immunity for lung megakaryocytes.

Megakaryocytes (nGFP+ CD41+) were sorted from PF4-nTnG lungs and bone marrow followed by mRNA isolation and sequencing. a, Relative mRNA expression is shown on a scale from low (green) to high (red). Three independent experiments (four mice each) were used for statistical analysis. Heatmap of all significantly differentially expressed genes (FDR <0.05). b, Read counts for megakaryocyte-related genes. These genes are found in both lung and bone marrow megakaryocytes, but some are underrepresented in lung megakaryocytes. c, d, Analysis of gene ontology biological processes related to genes that are downregulated (c) or upregulated (d) in lung megakaryocytes. The top 20 biological processes are shown. The vertical axis represents gene ontology categories, and the horizontal axis indicates the number of genes in each ontology category. e, f, Read counts for TLR gene pathways (e) and chemokines (f) that were overexpressed in lung megakaryocytes. FPKM, fragments per kilobase of exon per million fragments mapped. gk, Lung megakaryocytes and progenitor populations are altered during infection. Flow cytometric analysis of nGFP+ cells from PF4-nTnG lungs 24 h after intratracheal administration of S. aureus (MRSA, 5 × 107 colony-forming units (c.f.u.)). CD41–APC was injected intravenously before lung digestion and staining with CD41–FITC. The number of cells in normal or infected lungs are shown for all nGFP+ cells (g), less mature cells (nGFP+ CD41; h), and mature cells (nGFP+ CD41+; i). j, k, Percentage of intravascular megakaryocytes (j) and extravascular megakaryocytes (k) in the mature population (nGFP+ CD41+). n = 4–6 mice per group.

Source data

Extended Data Figure 5 Platelet reconstitution after lung transplantation with or without TPO injection.

Blood was collected from the mandibular vein every week following lung transplantation. After transplantation, a group of mice (red and orange) received TPO injection (250 mg kg−1, days 3 and 40). The other group was left untreated (blue and purple). Some mice in each group showed sustained platelet production for more than 3 months (blue and red). In the other mice (purple and orange), the platelet production was lower and transient (less than 3 months). The percentages of mice in each group are indicated. Data from individual mice (a, c, e, g) or group averages (b, d, f, h) are plotted. ad, i, j, Percentage of donor-derived platelets. Percentage was analysed by FACS, counting the tomato+ platelets (CD41+ FSCsmall gate). eh, k, Overall platelet counts in the peripheral blood. j, k, Plots from mice with 10 months of sustained platelet production. i, Percentage of tomato+ platelets in control lung transplants (n = 4–6). l, Colour code for the different lung transplant groups according to lung origin (donor), recipient mouse, treatment received (with or without TPO) and observed response (sustained or transient).

Source data

Extended Data Figure 6 Characterization of platelets produced after lung transplantation.

a, b, Flow cytometric analysis of tomato+ platelets observed in the blood and stained with antibodies against CD41, CD42d, GPVI and c-Mpl. Blood from PF4-tomato mice (a) or c-mpl−/− mice that had received PF4-tomato lung transplants (b). c, Experimental schema for platelet activation. d, Flow cytometric analysis of tomato+ platelets after stimulation with thrombin (10 nM) stained with antibody against CD62P. e, Percentage of CD62P+ platelets before and after thrombin activation. Ctrl, PF4-tomato; Lung tx, PF4-tomato lungs transplanted into c-mpl−/− mice. Mean ± s.d. are presented (n = 2–3 mice per group). Unpaired t-test: **P < 0.01, ***P < 0.001

Source data

Extended Data Figure 7 Lung and bone marrow analysis of transplanted mice.

Mice with sustained production of lung-derived platelets were killed at least 3 months after lung transplantation. a, Representative 2PIVM image of a PF4-tomato lung after transplantation into a c-mpl−/− mouse. b, Representative 2PIVM image of flushed bone marrow cells from PF4-tomato and c-mpl−/− mice, and wild-type and c-mpl−/− mice transplanted with PF4-tomato lungs. c, Experimental schema for transplantation of mTmG lungs into c-mpl−/− mice. Blood was collected from the mandibular vein every 2 weeks to test for donor-derived platelets (tomato+ platelets) and measure overall blood platelet counts. d, Percentage of donor-derived platelets analysed by FACS counting of tomato+ events in the CD41+ FSCsmall gate. e, Platelet counts in peripheral blood determined by CBC. d, e, Mean ± s.e.m. are presented. fl, Bone marrow cells from mTmG mice (D), c-mpl−/− mice (R), or c-mpl−/− mice transplanted with mTmG lungs (Tx) that showed sustained donor-derived platelet production for 3 months were analysed. Population frequencies within the CD45+ compartment were measured for myeloid progenitors (f, MP: Lin Sca-1 c-Kit+), MkPs (g), LSK cells (h, Lin Sca-1+ c-Kit+), LT-HSCs (i), ST-HSCs (j), MPP2s (k) and MPP3/4s (l). m, Population frequencies within the LSK compartment from indicated groups. np, Total cell populations (grey), donor origin tomato+ cells (red), and per cent tomato+ cells (above bars) in bone marrow (n), recipient native lung (right lung; o) and spleen (p). Mean ± s.d. are presented (n = 2–3 mice per group). Unpaired t-test: *P < 0.05, **P < 0.01, ***P < 0.001.

Source data

Extended Data Figure 8 Lung haematopoietic progenitors are extravascular and have multi-lineage capabilities.

a, Representative spleen FACS plots of haematopoietic progenitors within the LSK compartment and the myeloid progenitor compartment (Lin Sca-1 c-Kit+). b, Cell counts of haematopoietic progenitor populations in the spleen (n = 6). ce, Lungs were perfused before digestion. c, Representative FACS plot of LSK and myeloid progenitor compartments with anterograde perfusion and with or without retrograde perfusion. d, e, Frequencies (d) and cell counts (e) of lung haematopoietic progenitor populations (n = 3). fh, CD45-APC mAb was injected intravenously via the tail vein 5 min before lung digestion and staining with CD45-FITC mAb. g, Haematopoietic progenitor populations were examined for labelling with injected CD45 mAb by flow cytometry. h, Percentage of CD45-FITC+ cells positive or negative (extravascular cells) for the intravenous CD45-APC mAb (n = 3–6). ik, Peripheral blood was analysed 2–3 months after transplantation of mTmG lungs into c-mpl−/− mice. i, Representative FACS plot of blood cell analysis. j, Percentage of lung-derived cells (Tom+ CD41) in the blood after transplantation. k, Percentage of B cells (CD19+), T cells (CD3+) or neutrophils (CD11b+ Ly6G+) in the lung-derived cells (Tom+ CD41). Mean ± s.e.m. are presented (n = 5 mice per group).

Source data

Extended Data Figure 9 Proposed schema of lung involvement in platelet biogenesis.

The role of the lungs in platelet biogenesis is twofold and occurs in two different compartments. a, Platelet production in the lung vasculature. After being released from the bone marrow or the spleen, proplatelets (a1) and megakaryocytes (a2) are retained in the lung vasculature, the first capillary bed encountered by any cell leaving the bone marrow, where proplatelet formation and extension and final platelet release are observed. b, Mature and immature megakaryocytes along with haematopoietic progenitors are found in the lung interstitium. In thrombocytopenic environments, haematopoietic progenitors from the lung migrate and restore bone marrow haematopoietic deficiencies.

Extended Data Table 1 Variables used to calculate the number and percentage of platelets produced by the lungs

Supplementary information

Supplementary Table 1

This file contains Supplementary Tables 1a-g. (XLSX 6873 kb)

Dynamic release of platelets in the lung vasculature

Lung 2PIVM in PF4-mTmG mice where PF4-Cre drives membrane GFP expression in MKs and platelets while all other cells are labelled with membrane tomato. Several examples are shown of large GFP+ MKs that enter the lung circulation and undergo proplatelet formation and extension. Scale bars and acquisition time are indicated. (MOV 8348 kb)

MKs with nuclei circulating in the lung vasculature

Lung 2PIVM in PF4-mTmG mice where PF4-Cre drives membrane GFP expression in MKs and platelets while all other cells are labelled with membrane tomato. Several examples are shown of large GFP+ MKs that enter the lung circulation and undergo proplatelet formation and extension. The evidence of a nucleus in the GFP+ cells is supported by the presence of a dark centre that appears inside the GFP+ cells. At the end of the process, when all the cytoplasm has been released, a naked nucleus is observed. Scale bars and acquisition time are indicated. (MOV 11544 kb)

MK nuclei circulating in the lung vasculature

Lung 2PIVM in PF4-nTnG mice where PF4-Cre drives nuclear GFP expression in MKs while all other cells are labelled with nuclear tomato. Depicted are several examples of mobile GFP+ nuclei circulating in the lung. Scale bars and acquisition time are indicated. (MOV 2962 kb)

Surface analysis of MKs and platelets in the lung

Surface-rendered 3D reconstruction of GFP+ MKs and platelets recorded during lung 2PIVM in a PF4-mTmG mouse. Note in example 2 that the nuclear volume is not included in the rendered GFP+ surface volume. (MOV 11097 kb)

Quantification of MKs releasing platelets

Lung 2PIVM in a PF4-mTmG mouse that includes 0.7 μm3 of lung volume. The number of MKs releasing platelets during this 2 hour video were counted (white circles). (MOV 13284 kb)

MKs releasing platelets in the lung are of extrapulmonary origin

a) Lung 2PIVM of mTmG lung (no Cre expression) transplanted into a PF4-mTmG recipient. Intravascular GFP+ MKs from the PF4-mTmG recipient (extrapulmonary) were observed releasing proplatelets. b) Reverse transplant (PF4-mTmG lung transplanted into mTmG recipient) shows extravascular MKs (GFP+), but no intravascular MKs or proplatelet formation. Scale bars and acquisition time are indicated. (MOV 15394 kb)

Proplatelet release by MKs in the BM

Calvarium BM 2PIVM in PF4-mTmG mice. The videos show extravascular MKs (GFP+) releasing proplatelets in the BM sinusoids (arrows). (MOV 28912 kb)

MK migration in the BM sinusoids

Calvarium BM 2PIVM in PF4-mTmG mice. The videos show large MKs (circled) entering the BM sinusoids and exiting the imaged BM space. (MOV 13384 kb)

MKs releasing proplatelets in the spleen

Spleen 2PIVM in PF4-mTmG mice. The videos show large extravascular MKs in the spleen (green circles = inactive MKs; white circles = MKs releasing proplatelets). The higher-power views show examples of extravascular MKs releasing proplatelets into the splenic sinusoids. (MOV 20319 kb)

Sessile MKs are observed in the lung interstitium

Lung 2PIVM in PF4-mTmG mice (examples 1 and 2) or PF4-tomato mice (examples 3 and 4) where PF4-Cre drives membrane GFP or cytoplasmic tomato expression in MKs and platelets. Shown are examples of large MKs observed in the lung interstitium that remain sessile during several hours of imaging (up to 4 hours). (MOV 24537 kb)

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Lefrançais, E., Ortiz-Muñoz, G., Caudrillier, A. et al. The lung is a site of platelet biogenesis and a reservoir for haematopoietic progenitors. Nature 544, 105–109 (2017). https://doi.org/10.1038/nature21706

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