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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2023-03-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/81656 |
| _version_ | 1827968199131398144 |
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| author | Hongzhe Li Sandro Bräunig Parashar Dhapolar Göran Karlsson Stefan Lang Stefan Scheding |
| author_facet | Hongzhe Li Sandro Bräunig Parashar Dhapolar Göran Karlsson Stefan Lang Stefan Scheding |
| author_sort | Hongzhe Li |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-09T18:18:27Z |
| format | Article |
| id | doaj.art-06b1fdfa9b2c4dd094f80e2739033bca |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-09T18:18:27Z |
| publishDate | 2023-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-06b1fdfa9b2c4dd094f80e2739033bca2023-04-12T15:43:05ZengeLife Sciences Publications LtdeLife2050-084X2023-03-011210.7554/eLife.81656Identification of phenotypically, functionally, and anatomically distinct stromal niche populations in human bone marrow based on single-cell RNA sequencingHongzhe Li0https://orcid.org/0000-0001-7788-878XSandro Bräunig1https://orcid.org/0000-0002-4418-0854Parashar Dhapolar2Göran Karlsson3Stefan Lang4Stefan Scheding5https://orcid.org/0000-0002-8005-9568Division of Molecular Hematology and Stem Cell Center, Lund University, Lund, SwedenDivision of Molecular Hematology and Stem Cell Center, Lund University, Lund, SwedenDivision of Molecular Hematology and Stem Cell Center, Lund University, Lund, SwedenDivision of Molecular Hematology and Stem Cell Center, Lund University, Lund, SwedenDivision of Molecular Hematology and Stem Cell Center, Lund University, Lund, SwedenDivision of Molecular Hematology and Stem Cell Center, Lund University, Lund, Sweden; Department of Hematology, Skåne University Hospital, Lund, SwedenHematopoiesis 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.https://elifesciences.org/articles/81656hematopoietic microenvironmenthuman bone marrowstromal stem/progenitor cellssingle-cell RNA sequencingdifferentiation hierarchyhematopoietic-stromal communication |
| spellingShingle | Hongzhe Li Sandro Bräunig Parashar Dhapolar Göran Karlsson Stefan Lang Stefan Scheding Identification of phenotypically, functionally, and anatomically distinct stromal niche populations in human bone marrow based on single-cell RNA sequencing eLife hematopoietic microenvironment human bone marrow stromal stem/progenitor cells single-cell RNA sequencing differentiation hierarchy hematopoietic-stromal communication |
| 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 | hematopoietic microenvironment human bone marrow stromal stem/progenitor cells single-cell RNA sequencing differentiation hierarchy hematopoietic-stromal communication |
| url | https://elifesciences.org/articles/81656 |
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