Deconvolution of the hematopoietic stem cell microenvironment reveals a high degree of specialization and conservation
Calvo, Isabel A
Viñado, Ana C
San Martin-Uriz, Patxi
Romero, Juan P
Quilez Agreda, Delia
Miñana Barrios, Marta
Tegner, Jesper N
KAUST DepartmentBioengineering Program, Biological and Environmental Sciences and Engineering Division (BESE), King Abdullah University of Science and Technology KAUST, Thuwal 23955, Saudi Arabia
Biological and Environmental Science and Engineering (BESE) Division
Computer, Electrical and Mathematical Science and Engineering (CEMSE) Division
Permanent link to this recordhttp://hdl.handle.net/10754/676688
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AbstractUnderstanding the regulation of normal and malignant human hematopoiesis requires comprehensive cell atlas of the hematopoietic stem cell (HSC) regulatory microenvironment. Here, we develop a tailored bioinformatic pipeline to integrate public and proprietary single-cell RNA sequencing (scRNA-seq) datasets. As a result, we robustly identify for the first time 14 intermediate cell states and 11 stages of differentiation in the endothelial and mesenchymal BM compartments, respectively. Our data provide the most comprehensive description to date of the murine HSC-regulatory microenvironment and suggest a higher level of specialization of the cellular circuits than previously anticipated. Furthermore, this deep characterization allows inferring conserved features in human, suggesting that the layers of microenvironmental regulation of hematopoiesis may also be shared between species. Our resource and methodology is a stepping-stone toward a comprehensive cell atlas of the BM microenvironment.
CitationYe, J., Calvo, I. A., Cenzano, I., Vilas, A., Martinez-de-Morentin, X., Lasaga, M., Alignani, D., Paiva, B., Viñado, A. C., San Martin-Uriz, P., Romero, J. P., Quilez Agreda, D., Miñana Barrios, M., Sancho-González, I., Todisco, G., Malcovati, L., Planell, N., Saez, B., Tegner, J. N., … Gomez-Cabrero, D. (2022). Deconvolution of the hematopoietic stem cell microenvironment reveals a high degree of specialization and conservation. IScience, 25(5), 104225. https://doi.org/10.1016/j.isci.2022.104225
SponsorsWe would like to thank the staff of the flow cytometry core, the advances genomic lab, and the animal facility at CIMA Universidad de Navarra for their invaluable technical and intellectual assistance. We are particularly grateful to the healthy volunteers who donated bone marrow tissue for this study. We also acknowledge Ali O. Balubaid’s help in writing. We would like to acknowledge Miguel Cocera-Fernandez’s contribution to the Graphical Abstract.
Funded by grants from The Spanish Government, through project PID2019-111192GA-I00 (MICINN) to DGC. Instituto de Salud Carlos III (ISCIII) and co-financed by FEDER: PI16/02024, PI17/00701 and PI19/01352, TRANSCAN EPICA AC16/00041, CIBERONC CB16/12/00489; Redes de Investigación Cooperativa (TERCEL RD16/0011/0005); Spanish Ministry of Economy, Industry and Competitivity (RTHALMY SAF2017-92632-EXP); Departamento de Salud, Gobierno de Navarra 40/2016 and Departamento de Desarrollo Económico y Empresarial (AGATA 0011-1411-2020-000010 and 0011-1411-2020-000013). The study was also supported by Cancer Research UK [C355/A26819] and Cancer Research UK, FCAECC and AIRC under the Accelerator Award Program (EDITOR), the Multiple Myeloma Research Foundation Networks of excellence 2017 Immunotherapy Program Grant Award, the International Myeloma Foundation (Brian van Novis), and Paula and Rodger Riney Foundation to FP. Instituto de Salud Carlos III (ISCIII) (PI17/01346 and PI20/00152), co-funded by the ERDF (A way to make Europe); FC-AECC (AIO16163636SAEZ); Gobierno de Navarra (0011-3638-2020-000011) co-funded by the ERDF through the Operative Program 2014–2020 of Navarra and Gobierno de Navarra (0011-3597-2020-000005) to BS. G.T. was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC), 5x1000 Program (Project #21267). IC was supported by Juan de la Cierva grant from Ministerio de Ciencia, Innovación y Universidades, Gobierno de España, Sara Borrell award from Instituto de Salud Carlos III (ISCIII) and Marie Curie grant (H2020-MSCA-IF-837491) from European Commission. ICA was supported by AECC predoctoral fellowship. NP was supported by Juan de la Cierva grant from Ministerio de Ciencia, Innovación y Universidades, Gobierno de España (FJC2019-042304-I). L.M. was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC) 5x1000 Program (Project #21267) and Investigator Grant 2017 (Project #20125), and by Cancer Research UK, FCAECC and AIRC Accelerator Award Program (Project #C355/A26819 and #22796).
PubMed Central IDPMC9046238
Except where otherwise noted, this item's license is described as NOTICE: this is the author’s version of a work that was accepted for publication in iScience. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in iScience, [25, 5, (2022-04-22)] DOI: 10.1016/j.isci.2022.104225 . © 2022. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
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