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Establishing a human bone marrow single cell reference atlas to study ageing and diseases
INTRODUCTION: Ageing in the human bone marrow is associated with immune function decline that results in the elderly being vulnerable to illnesses. A comprehensive healthy bone marrow consensus atlas can serve as a reference to study the immunological changes associated with ageing, and to identify...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10050687/ https://www.ncbi.nlm.nih.gov/pubmed/37006302 http://dx.doi.org/10.3389/fimmu.2023.1127879 |
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author | Lee, Nicole Yee Shin Li, Mengwei Ang, Kok Siong Chen, Jinmiao |
author_facet | Lee, Nicole Yee Shin Li, Mengwei Ang, Kok Siong Chen, Jinmiao |
author_sort | Lee, Nicole Yee Shin |
collection | PubMed |
description | INTRODUCTION: Ageing in the human bone marrow is associated with immune function decline that results in the elderly being vulnerable to illnesses. A comprehensive healthy bone marrow consensus atlas can serve as a reference to study the immunological changes associated with ageing, and to identify and study abnormal cell states. METHODS: We collected publicly available single cell transcriptomic data of 145 healthy samples encompassing a wide spectrum of ages ranging from 2 to 84 years old to construct our human bone marrow atlas. The final atlas has 673,750 cells and 54 annotated cell types. RESULTS: We first characterised the changes in cell population sizes with respect to age and the corresponding changes in gene expression and pathways. Overall, we found significant age-associated changes in the lymphoid lineage cells. The naïve CD8(+) T cell population showed significant shrinkage with ageing while the effector/memory CD4(+) T cells increased in proportion. We also found an age-correlated decline in the common lymphoid progenitor population, in line with the commonly observed myeloid skew in haematopoiesis among the elderly. We then employed our cell type-specific ageing gene signatures to develop a machine learning model that predicts the biological age of bone marrow samples, which we then applied to healthy individuals and those with blood diseases. Finally, we demonstrated how to identify abnormal cell states by mapping disease samples onto the atlas. We accurately identified abnormal plasma cells and erythroblasts in multiple myeloma samples, and abnormal cells in acute myeloid leukaemia samples. DISCUSSION: The bone marrow is the site of haematopoiesis, a highly important bodily process. We believe that our healthy bone marrow atlas is a valuable reference for studying bone marrow processes and bone marrow-related diseases. It can be mined for novel discoveries, as well as serve as a reference scaffold for mapping samples to identify and investigate abnormal cells. |
format | Online Article Text |
id | pubmed-10050687 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-100506872023-03-30 Establishing a human bone marrow single cell reference atlas to study ageing and diseases Lee, Nicole Yee Shin Li, Mengwei Ang, Kok Siong Chen, Jinmiao Front Immunol Immunology INTRODUCTION: Ageing in the human bone marrow is associated with immune function decline that results in the elderly being vulnerable to illnesses. A comprehensive healthy bone marrow consensus atlas can serve as a reference to study the immunological changes associated with ageing, and to identify and study abnormal cell states. METHODS: We collected publicly available single cell transcriptomic data of 145 healthy samples encompassing a wide spectrum of ages ranging from 2 to 84 years old to construct our human bone marrow atlas. The final atlas has 673,750 cells and 54 annotated cell types. RESULTS: We first characterised the changes in cell population sizes with respect to age and the corresponding changes in gene expression and pathways. Overall, we found significant age-associated changes in the lymphoid lineage cells. The naïve CD8(+) T cell population showed significant shrinkage with ageing while the effector/memory CD4(+) T cells increased in proportion. We also found an age-correlated decline in the common lymphoid progenitor population, in line with the commonly observed myeloid skew in haematopoiesis among the elderly. We then employed our cell type-specific ageing gene signatures to develop a machine learning model that predicts the biological age of bone marrow samples, which we then applied to healthy individuals and those with blood diseases. Finally, we demonstrated how to identify abnormal cell states by mapping disease samples onto the atlas. We accurately identified abnormal plasma cells and erythroblasts in multiple myeloma samples, and abnormal cells in acute myeloid leukaemia samples. DISCUSSION: The bone marrow is the site of haematopoiesis, a highly important bodily process. We believe that our healthy bone marrow atlas is a valuable reference for studying bone marrow processes and bone marrow-related diseases. It can be mined for novel discoveries, as well as serve as a reference scaffold for mapping samples to identify and investigate abnormal cells. Frontiers Media S.A. 2023-03-15 /pmc/articles/PMC10050687/ /pubmed/37006302 http://dx.doi.org/10.3389/fimmu.2023.1127879 Text en Copyright © 2023 Lee, Li, Ang and Chen https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Lee, Nicole Yee Shin Li, Mengwei Ang, Kok Siong Chen, Jinmiao Establishing a human bone marrow single cell reference atlas to study ageing and diseases |
title | Establishing a human bone marrow single cell reference atlas to study ageing and diseases |
title_full | Establishing a human bone marrow single cell reference atlas to study ageing and diseases |
title_fullStr | Establishing a human bone marrow single cell reference atlas to study ageing and diseases |
title_full_unstemmed | Establishing a human bone marrow single cell reference atlas to study ageing and diseases |
title_short | Establishing a human bone marrow single cell reference atlas to study ageing and diseases |
title_sort | establishing a human bone marrow single cell reference atlas to study ageing and diseases |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10050687/ https://www.ncbi.nlm.nih.gov/pubmed/37006302 http://dx.doi.org/10.3389/fimmu.2023.1127879 |
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