Deconvolution of the hematopoietic stem cell microenvironment reveals a high degree of specialization and conservation

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 (scR...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2022-05-01
Series:iScience
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004222004953
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author 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
author_facet 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
author_sort Jin Ye
collection DOAJ
description 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.
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spelling doaj.art-ccde1bb022e24ec1a1f2e788e69807b22022-12-22T02:25:52ZengElsevieriScience2589-00422022-05-01255104225Deconvolution of the hematopoietic stem cell microenvironment reveals a high degree of specialization and conservationJin Ye0Isabel A. Calvo1Itziar Cenzano2Amaia Vilas3Xabier Martinez-de-Morentin4Miren Lasaga5Diego Alignani6Bruno Paiva7Ana C. Viñado8Patxi San Martin-Uriz9Juan P. Romero10Delia Quilez Agreda11Marta Miñana Barrios12Ignacio Sancho-González13Gabriele Todisco14Luca Malcovati15Nuria Planell16Borja Saez17Jesper N. Tegner18Felipe Prosper19David Gomez-Cabrero20Bioscience Program, Biological and Environmental Sciences and Engineering Division (BESE), King Abdullah University of Science and Technology KAUST, Thuwal 23955, Saudi ArabiaUniversidad 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, SpainUniversidad de Navarra, CIMA, Hematology-Oncology Program, Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Navarra, SpainUniversidad 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, SpainNavarrabiomed, ComplejoHospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), IdiSNA, Pamplona, 31008 Navarra, SpainNavarrabiomed, ComplejoHospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), IdiSNA, Pamplona, 31008 Navarra, SpainUniversidad 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, SpainUniversidad 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, SpainUniversidad 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, SpainUniversidad de Navarra, CIMA, Hematology-Oncology Program, Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Navarra, SpainUniversidad de Navarra, CIMA, Hematology-Oncology Program, Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Navarra, SpainHospital Reina Sofía de Tudela, 31500 Navarra, SpainHospital Reina Sofía de Tudela, 31500 Navarra, SpainHospital Reina Sofía de Tudela, 31500 Navarra, SpainDepartment 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, SwedenDepartment of Molecular Medicine, University of Pavia & Unit of Precision Hematology Oncology, IRCCS S. Matteo Hospital Foundation, 27100 Pavia, ItalyNavarrabiomed, ComplejoHospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), IdiSNA, Pamplona, 31008 Navarra, SpainUniversidad 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 authorBioscience 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 authorUniversidad 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 authorBioscience 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 authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004222004953Biological sciencesStem cells researchOmicsTranscriptomics
spellingShingle 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
Deconvolution of the hematopoietic stem cell microenvironment reveals a high degree of specialization and conservation
iScience
Biological sciences
Stem cells research
Omics
Transcriptomics
title Deconvolution of the hematopoietic stem cell microenvironment reveals a high degree of specialization and conservation
title_full Deconvolution of the hematopoietic stem cell microenvironment reveals a high degree of specialization and conservation
title_fullStr Deconvolution of the hematopoietic stem cell microenvironment reveals a high degree of specialization and conservation
title_full_unstemmed Deconvolution of the hematopoietic stem cell microenvironment reveals a high degree of specialization and conservation
title_short Deconvolution of the hematopoietic stem cell microenvironment reveals a high degree of specialization and conservation
title_sort deconvolution of the hematopoietic stem cell microenvironment reveals a high degree of specialization and conservation
topic Biological sciences
Stem cells research
Omics
Transcriptomics
url http://www.sciencedirect.com/science/article/pii/S2589004222004953
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