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Identification of phenotypically, functionally, and anatomically distinct stromal niche populations in human bone marrow based on single-cell RNA sequencing

Hematopoiesis is regulated by the bone marrow (BM) stroma. However, cellular identities and functions of the different BM stromal elements in humans remain poorly defined. Based on single-cell RNA sequencing (scRNAseq), we systematically characterized the human non-hematopoietic BM stromal compartme...

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Autores principales: Li, Hongzhe, Bräunig, Sandro, Dhapolar, Parashar, Karlsson, Göran, Lang, Stefan, Scheding, Stefan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10097421/
https://www.ncbi.nlm.nih.gov/pubmed/36876630
http://dx.doi.org/10.7554/eLife.81656
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author Li, Hongzhe
Bräunig, Sandro
Dhapolar, Parashar
Karlsson, Göran
Lang, Stefan
Scheding, Stefan
author_facet Li, Hongzhe
Bräunig, Sandro
Dhapolar, Parashar
Karlsson, Göran
Lang, Stefan
Scheding, Stefan
author_sort Li, Hongzhe
collection PubMed
description Hematopoiesis is regulated by the bone marrow (BM) stroma. However, cellular identities and functions of the different BM stromal elements in humans remain poorly defined. Based on single-cell RNA sequencing (scRNAseq), we systematically characterized the human non-hematopoietic BM stromal compartment and we investigated stromal cell regulation principles based on the RNA velocity analysis using scVelo and studied the interactions between the human BM stromal cells and hematopoietic cells based on ligand-receptor (LR) expression using CellPhoneDB. scRNAseq led to the identification of six transcriptionally and functionally distinct stromal cell populations. Stromal cell differentiation hierarchy was recapitulated based on RNA velocity analysis and in vitro proliferation capacities and differentiation potentials. Potential key factors that might govern the transition from stem and progenitor cells to fate-committed cells were identified. In situ localization analysis demonstrated that different stromal cells were localized in different niches in the bone marrow. In silico cell-cell communication analysis further predicted that different stromal cell types might regulate hematopoiesis through distinct mechanisms. These findings provide the basis for a comprehensive understanding of the cellular complexity of the human BM microenvironment and the intricate stroma-hematopoiesis crosstalk mechanisms, thus refining our current view on human hematopoietic niche organization.
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spelling pubmed-100974212023-04-13 Identification of phenotypically, functionally, and anatomically distinct stromal niche populations in human bone marrow based on single-cell RNA sequencing Li, Hongzhe Bräunig, Sandro Dhapolar, Parashar Karlsson, Göran Lang, Stefan Scheding, Stefan eLife Stem Cells and Regenerative Medicine Hematopoiesis is regulated by the bone marrow (BM) stroma. However, cellular identities and functions of the different BM stromal elements in humans remain poorly defined. Based on single-cell RNA sequencing (scRNAseq), we systematically characterized the human non-hematopoietic BM stromal compartment and we investigated stromal cell regulation principles based on the RNA velocity analysis using scVelo and studied the interactions between the human BM stromal cells and hematopoietic cells based on ligand-receptor (LR) expression using CellPhoneDB. scRNAseq led to the identification of six transcriptionally and functionally distinct stromal cell populations. Stromal cell differentiation hierarchy was recapitulated based on RNA velocity analysis and in vitro proliferation capacities and differentiation potentials. Potential key factors that might govern the transition from stem and progenitor cells to fate-committed cells were identified. In situ localization analysis demonstrated that different stromal cells were localized in different niches in the bone marrow. In silico cell-cell communication analysis further predicted that different stromal cell types might regulate hematopoiesis through distinct mechanisms. These findings provide the basis for a comprehensive understanding of the cellular complexity of the human BM microenvironment and the intricate stroma-hematopoiesis crosstalk mechanisms, thus refining our current view on human hematopoietic niche organization. eLife Sciences Publications, Ltd 2023-03-06 /pmc/articles/PMC10097421/ /pubmed/36876630 http://dx.doi.org/10.7554/eLife.81656 Text en © 2023, Li et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Stem Cells and Regenerative Medicine
Li, Hongzhe
Bräunig, Sandro
Dhapolar, Parashar
Karlsson, Göran
Lang, Stefan
Scheding, Stefan
Identification of phenotypically, functionally, and anatomically distinct stromal niche populations in human bone marrow based on single-cell RNA sequencing
title Identification of phenotypically, functionally, and anatomically distinct stromal niche populations in human bone marrow based on single-cell RNA sequencing
title_full Identification of phenotypically, functionally, and anatomically distinct stromal niche populations in human bone marrow based on single-cell RNA sequencing
title_fullStr Identification of phenotypically, functionally, and anatomically distinct stromal niche populations in human bone marrow based on single-cell RNA sequencing
title_full_unstemmed Identification of phenotypically, functionally, and anatomically distinct stromal niche populations in human bone marrow based on single-cell RNA sequencing
title_short Identification of phenotypically, functionally, and anatomically distinct stromal niche populations in human bone marrow based on single-cell RNA sequencing
title_sort identification of phenotypically, functionally, and anatomically distinct stromal niche populations in human bone marrow based on single-cell rna sequencing
topic Stem Cells and Regenerative Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10097421/
https://www.ncbi.nlm.nih.gov/pubmed/36876630
http://dx.doi.org/10.7554/eLife.81656
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