iScience (May 2022)
Deconvolution of the hematopoietic stem cell microenvironment reveals a high degree of specialization and conservation
- Jin Ye,
- Isabel A. Calvo,
- Itziar Cenzano,
- Amaia Vilas,
- Xabier Martinez-de-Morentin,
- Miren Lasaga,
- Diego Alignani,
- Bruno Paiva,
- Ana C. Viñado,
- Patxi San Martin-Uriz,
- Juan P. Romero,
- Delia Quilez Agreda,
- Marta Miñana Barrios,
- Ignacio Sancho-González,
- Gabriele Todisco,
- Luca Malcovati,
- Nuria Planell,
- Borja Saez,
- Jesper N. Tegner,
- Felipe Prosper,
- David Gomez-Cabrero
Affiliations
- Jin Ye
- Bioscience Program, Biological and Environmental Sciences and Engineering Division (BESE), King Abdullah University of Science and Technology KAUST, Thuwal 23955, Saudi Arabia
- Isabel A. Calvo
- Universidad de Navarra, CIMA, Hematology-Oncology Program, Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Navarra, Spain; Centro de Investigación Biomédica en Red de Cáncer, CIBERONC, Madrid, Spain
- Itziar Cenzano
- Universidad de Navarra, CIMA, Hematology-Oncology Program, Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Navarra, Spain
- Amaia Vilas
- Universidad de Navarra, CIMA, Hematology-Oncology Program, Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Navarra, Spain; Centro de Investigación Biomédica en Red de Cáncer, CIBERONC, Madrid, Spain
- Xabier Martinez-de-Morentin
- Navarrabiomed, ComplejoHospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), IdiSNA, Pamplona, 31008 Navarra, Spain
- Miren Lasaga
- Navarrabiomed, ComplejoHospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), IdiSNA, Pamplona, 31008 Navarra, Spain
- Diego Alignani
- Universidad de Navarra, CIMA, Hematology-Oncology Program, Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Navarra, Spain; Centro de Investigación Biomédica en Red de Cáncer, CIBERONC, Madrid, Spain
- Bruno Paiva
- Universidad de Navarra, CIMA, Hematology-Oncology Program, Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Navarra, Spain; Centro de Investigación Biomédica en Red de Cáncer, CIBERONC, Madrid, Spain
- Ana C. Viñado
- Universidad de Navarra, CIMA, Hematology-Oncology Program, Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Navarra, Spain; Centro de Investigación Biomédica en Red de Cáncer, CIBERONC, Madrid, Spain
- Patxi San Martin-Uriz
- Universidad de Navarra, CIMA, Hematology-Oncology Program, Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Navarra, Spain
- Juan P. Romero
- Universidad de Navarra, CIMA, Hematology-Oncology Program, Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Navarra, Spain
- Delia Quilez Agreda
- Hospital Reina Sofía de Tudela, 31500 Navarra, Spain
- Marta Miñana Barrios
- Hospital Reina Sofía de Tudela, 31500 Navarra, Spain
- Ignacio Sancho-González
- Hospital Reina Sofía de Tudela, 31500 Navarra, Spain
- Gabriele Todisco
- Department of Molecular Medicine, University of Pavia & Unit of Precision Hematology Oncology, IRCCS S. Matteo Hospital Foundation, 27100 Pavia, Italy; Department of Medicine, Center for Hematology and Regenerative Medicine, Karolinska Institutet, 17177 Stockholm, Sweden
- Luca Malcovati
- Department of Molecular Medicine, University of Pavia & Unit of Precision Hematology Oncology, IRCCS S. Matteo Hospital Foundation, 27100 Pavia, Italy
- Nuria Planell
- Navarrabiomed, ComplejoHospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), IdiSNA, Pamplona, 31008 Navarra, Spain
- Borja Saez
- Universidad de Navarra, CIMA, Hematology-Oncology Program, Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Navarra, Spain; Centro de Investigación Biomédica en Red de Cáncer, CIBERONC, Madrid, Spain; Corresponding author
- Jesper N. Tegner
- Bioscience Program, Biological and Environmental Sciences and Engineering Division (BESE), King Abdullah University of Science and Technology KAUST, Thuwal 23955, Saudi Arabia; Department of Medicine, Centre for Molecular Medicine, Karolinska Institutet, 17177 Stockholm, Stockholm, Sweden; Computer, Electrical, and Mathematical Sciences and Engineering Division (CEMSE), King Abdullah University of Science and Technology KAUST, Thuwal 23955, Saudi Arabia; Bioengineering Program, Biological and Environmental Sciences and Engineering Division (BESE), King Abdullah University of Science and Technology KAUST, Thuwal 23955, Saudi Arabia; Corresponding author
- Felipe Prosper
- Universidad de Navarra, CIMA, Hematology-Oncology Program, Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Navarra, Spain; Centro de Investigación Biomédica en Red de Cáncer, CIBERONC, Madrid, Spain; Service of Hematology and Cell Therapy, Clínica Universidad de Navarra; CCUN, Pamplona, Navarra, 31008; Spain; Corresponding author
- David Gomez-Cabrero
- Bioscience Program, Biological and Environmental Sciences and Engineering Division (BESE), King Abdullah University of Science and Technology KAUST, Thuwal 23955, Saudi Arabia; Navarrabiomed, ComplejoHospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), IdiSNA, Pamplona, 31008 Navarra, Spain; Department of Medicine, Centre for Molecular Medicine, Karolinska Institutet, 17177 Stockholm, Stockholm, Sweden; Centre for Host Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King’s College, London WC2R 2LS, UK; Bioengineering Program, Biological and Environmental Sciences and Engineering Division (BESE), King Abdullah University of Science and Technology KAUST, Thuwal 23955, Saudi Arabia; Corresponding author
- Journal volume & issue
-
Vol. 25,
no. 5
p. 104225
Abstract
Summary: 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.
