Key Points
-
Functional hematopoietic stem cells with unique gene signatures reside in the adult human lung.
-
These cells contribute to the pool of hematopoietic stem cells mobilized for stem cell transplantation.
Visual Abstract
Abstract
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
Acknowledgments
The authors thank Donor Network West, Michael Matthay (University of California San Francisco ), and the Nina Ireland Program for Lung Health (UCSF) for providing human lung tissue from deceased organ donors.
This work was supported by an International Anesthesia Researach Society (IARS) Mentored Research Award to C.C., the Deutsche Forschungsgemeinschaft Research Fellowships to C.C. (CO 2096/1-1) and N.M. (ME 5209/1-1), Bakar UCSF ImmunoX support to A.J.C, a Wellcome-Royal Society Sir Henry Dale Fellowship (107630/Z/15/Z) and funding in part by the Wellcome Trust [203151/Z/16/Z, 203151/A/16/Z] and the United Kingdom Research and Innovation (UKRI) Medical Research Council to E.L., and National Institutes of Health (NIH), National Heart, Lung, and Blood Institute grant R35HL161241 to M.R.L. Sequencing was performed at the UCSF Center for Advanced Technology, supported by the UCSF Program for Breakthrough Biomedical Research, Research Ressource Program Institutional Matching Instrumentation Award, and NIH, Office of the Director 1S10OD028511-01 grants.
Authorship
Contribution: C.C. designed and conducted experiments, analyzed the data, and wrote the manuscript; M.M. designed and conducted experiments; J.T., B.S., U.V., and A.J.C. assisted in designing and conducting experiments and helped analyzing the data; H.W. and M.N. helped analyzing the data; S.J.C., L.Q., J.J.T., and M.D.G. assisted in conducting experiments; A.D.L. provided human apheresis blood samples; E.P., E.L., and N.M. assisted in designing experiments, provided technical expertise with hematopoietic progenitor analyses, and provided editorial support on the manuscript; and M.R.L. designed the experiments, supervised the study, and wrote the manuscript.
Conflict-of-interest disclosure: The authors declare no competing financial interests.
Correspondence: Mark R. Looney, Department of Medicine, University of California San Francisco, 513 Parnassus Ave, HSE 1355A, San Francisco, CA 94143-0130; email: mark.looney@ucsf.edu.
De redactie van Blood geeft ook een interessant commentaar op de studie van de universiteit van San Francisco: Breathing life into the hematopoietic potential of the lung
References
Author notes
Sequencing data have been deposited in the Gene Expression Omnibus database (accession code GSE255687).
There are no restrictions on data availability or use. The Human Lung Cell Atlas is publicly available data set that can be accessed at https://azimuth.hubmapconsortium.org/references/human_lung_v2/. Codes used in this study are available on request from the corresponding author, Mark R. Looney (mark.looney@ucsf.edu).
The online version of this article contains a data supplement.
There is a Blood Commentary on this article in this issue.
The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked “advertisement” in accordance with 18 USC section 1734.
Plaats een reactie ...
Reageer op "Bloedcellen: Onze longen ondersteunen ons beenmerg in het maken van rode bloedcellen, bloedplaatjes en immuuncellen."