Deconvolution of the hematopoietic stem cell microenvironment reveals a high degree of specialization and conservation
Understanding 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. ; We 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 ...
