Decoding lymphomyeloid divergence and immune hyporesponsiveness in G-CSF-primed human bone marrow by single-cell RNA-seq
Abstract Granulocyte colony-stimulating factor (G-CSF) has been widely used to mobilize bone marrow hematopoietic stem/progenitor cells for transplantation in the treatment of hematological malignancies for decades. Additionally, G-CSF is also accepted as an essential mediator in immune regulation,...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-06-01
|
| Series: | Cell Discovery |
| Online Access: | https://doi.org/10.1038/s41421-022-00417-y |
| _version_ | 1818250244491575296 |
|---|---|
| author | Guoju You Man Zhang Zhilei Bian Huidong Guo Zhengyang Xu Yanli Ni Yu Lan Wen Yue Yandong Gong Yingjun Chang Xiaojun Huang Bing Liu |
| author_facet | Guoju You Man Zhang Zhilei Bian Huidong Guo Zhengyang Xu Yanli Ni Yu Lan Wen Yue Yandong Gong Yingjun Chang Xiaojun Huang Bing Liu |
| author_sort | Guoju You |
| collection | DOAJ |
| description | Abstract Granulocyte colony-stimulating factor (G-CSF) has been widely used to mobilize bone marrow hematopoietic stem/progenitor cells for transplantation in the treatment of hematological malignancies for decades. Additionally, G-CSF is also accepted as an essential mediator in immune regulation, leading to reduced graft-versus-host disease following transplantation. Despite the important clinical roles of G-CSF, a comprehensive, unbiased, and high-resolution survey into the cellular and molecular ecosystem of the human G-CSF-primed bone marrow (G-BM) is lacking so far. Here, we employed single-cell RNA sequencing to profile hematopoietic cells in human bone marrow from two healthy donors before and after 5-day G-CSF administration. Through unbiased bioinformatics analysis, our data systematically showed the alterations in the transcriptional landscape of hematopoietic cells in G-BM, and revealed that G-CSF-induced myeloid-biased differentiation initiated from the stage of lymphoid-primed multipotent progenitors. We also illustrated the cellular and molecular basis of hyporesponsiveness of T cells and natural killer (NK) cells caused by G-CSF stimulation, including the potential direct mechanisms and indirect regulations mediated by ligand–receptor interactions. Taken together, our data extend the understanding of lymphomyeloid divergence and potential mechanisms involved in hyporesponsiveness of T and NK cells in human G-BM, which might provide basis for optimization of stem cell transplantation in hematological malignancy treatment. |
| first_indexed | 2024-12-12T15:49:18Z |
| format | Article |
| id | doaj.art-ef3095779cb3436e97ccc3f0db8c09f9 |
| institution | Directory Open Access Journal |
| issn | 2056-5968 |
| language | English |
| last_indexed | 2024-12-12T15:49:18Z |
| publishDate | 2022-06-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Discovery |
| spelling | doaj.art-ef3095779cb3436e97ccc3f0db8c09f92022-12-22T00:19:40ZengNature Publishing GroupCell Discovery2056-59682022-06-018111510.1038/s41421-022-00417-yDecoding lymphomyeloid divergence and immune hyporesponsiveness in G-CSF-primed human bone marrow by single-cell RNA-seqGuoju You0Man Zhang1Zhilei Bian2Huidong Guo3Zhengyang Xu4Yanli Ni5Yu Lan6Wen Yue7Yandong Gong8Yingjun Chang9Xiaojun Huang10Bing Liu11State Key Laboratory of Primate Biomedical Research, State Key Laboratory of Experimental Hematology, School of Medicine, Tsinghua UniversityState Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military SciencesKey Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan UniversityPeking University People’s Hospital & Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell TransplantationState Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military SciencesState Key Laboratory of Experimental Hematology, State Key Laboratory of Primate Biomedical Research, Institute of Hematology, Fifth Medical Center of Chinese PLA General HospitalKey Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan UniversityState Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military SciencesKey Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan UniversityPeking University People’s Hospital & Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell TransplantationPeking University People’s Hospital & Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell TransplantationState Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military SciencesAbstract Granulocyte colony-stimulating factor (G-CSF) has been widely used to mobilize bone marrow hematopoietic stem/progenitor cells for transplantation in the treatment of hematological malignancies for decades. Additionally, G-CSF is also accepted as an essential mediator in immune regulation, leading to reduced graft-versus-host disease following transplantation. Despite the important clinical roles of G-CSF, a comprehensive, unbiased, and high-resolution survey into the cellular and molecular ecosystem of the human G-CSF-primed bone marrow (G-BM) is lacking so far. Here, we employed single-cell RNA sequencing to profile hematopoietic cells in human bone marrow from two healthy donors before and after 5-day G-CSF administration. Through unbiased bioinformatics analysis, our data systematically showed the alterations in the transcriptional landscape of hematopoietic cells in G-BM, and revealed that G-CSF-induced myeloid-biased differentiation initiated from the stage of lymphoid-primed multipotent progenitors. We also illustrated the cellular and molecular basis of hyporesponsiveness of T cells and natural killer (NK) cells caused by G-CSF stimulation, including the potential direct mechanisms and indirect regulations mediated by ligand–receptor interactions. Taken together, our data extend the understanding of lymphomyeloid divergence and potential mechanisms involved in hyporesponsiveness of T and NK cells in human G-BM, which might provide basis for optimization of stem cell transplantation in hematological malignancy treatment.https://doi.org/10.1038/s41421-022-00417-y |
| spellingShingle | Guoju You Man Zhang Zhilei Bian Huidong Guo Zhengyang Xu Yanli Ni Yu Lan Wen Yue Yandong Gong Yingjun Chang Xiaojun Huang Bing Liu Decoding lymphomyeloid divergence and immune hyporesponsiveness in G-CSF-primed human bone marrow by single-cell RNA-seq Cell Discovery |
| title | Decoding lymphomyeloid divergence and immune hyporesponsiveness in G-CSF-primed human bone marrow by single-cell RNA-seq |
| title_full | Decoding lymphomyeloid divergence and immune hyporesponsiveness in G-CSF-primed human bone marrow by single-cell RNA-seq |
| title_fullStr | Decoding lymphomyeloid divergence and immune hyporesponsiveness in G-CSF-primed human bone marrow by single-cell RNA-seq |
| title_full_unstemmed | Decoding lymphomyeloid divergence and immune hyporesponsiveness in G-CSF-primed human bone marrow by single-cell RNA-seq |
| title_short | Decoding lymphomyeloid divergence and immune hyporesponsiveness in G-CSF-primed human bone marrow by single-cell RNA-seq |
| title_sort | decoding lymphomyeloid divergence and immune hyporesponsiveness in g csf primed human bone marrow by single cell rna seq |
| url | https://doi.org/10.1038/s41421-022-00417-y |
| work_keys_str_mv | AT guojuyou decodinglymphomyeloiddivergenceandimmunehyporesponsivenessingcsfprimedhumanbonemarrowbysinglecellrnaseq AT manzhang decodinglymphomyeloiddivergenceandimmunehyporesponsivenessingcsfprimedhumanbonemarrowbysinglecellrnaseq AT zhileibian decodinglymphomyeloiddivergenceandimmunehyporesponsivenessingcsfprimedhumanbonemarrowbysinglecellrnaseq AT huidongguo decodinglymphomyeloiddivergenceandimmunehyporesponsivenessingcsfprimedhumanbonemarrowbysinglecellrnaseq AT zhengyangxu decodinglymphomyeloiddivergenceandimmunehyporesponsivenessingcsfprimedhumanbonemarrowbysinglecellrnaseq AT yanlini decodinglymphomyeloiddivergenceandimmunehyporesponsivenessingcsfprimedhumanbonemarrowbysinglecellrnaseq AT yulan decodinglymphomyeloiddivergenceandimmunehyporesponsivenessingcsfprimedhumanbonemarrowbysinglecellrnaseq AT wenyue decodinglymphomyeloiddivergenceandimmunehyporesponsivenessingcsfprimedhumanbonemarrowbysinglecellrnaseq AT yandonggong decodinglymphomyeloiddivergenceandimmunehyporesponsivenessingcsfprimedhumanbonemarrowbysinglecellrnaseq AT yingjunchang decodinglymphomyeloiddivergenceandimmunehyporesponsivenessingcsfprimedhumanbonemarrowbysinglecellrnaseq AT xiaojunhuang decodinglymphomyeloiddivergenceandimmunehyporesponsivenessingcsfprimedhumanbonemarrowbysinglecellrnaseq AT bingliu decodinglymphomyeloiddivergenceandimmunehyporesponsivenessingcsfprimedhumanbonemarrowbysinglecellrnaseq |