Characterization of gene regulatory networks underlying key properties in human hematopoietic stem cell ontogeny
Abstract Human hematopoiesis starts at early yolk sac and undergoes site- and stage-specific changes over development. The intrinsic mechanism underlying property changes in hematopoiesis ontogeny remains poorly understood. Here, we analyzed single-cell transcriptome of human primary hematopoietic s...
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| Format: | Article |
| Language: | English |
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SpringerOpen
2024-04-01
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| Series: | Cell Regeneration |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13619-024-00192-z |
| _version_ | 1797199404463030272 |
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| author | Fei Li Yanling Zhu Tianyu Wang Jun Tang Yuhua Huang Jiaming Gu Yuchan Mai Mingquan Wang Zhishuai Zhang Jiaying Ning Baoqiang Kang Junwei Wang Tiancheng Zhou Yazhou Cui Guangjin Pan |
| author_facet | Fei Li Yanling Zhu Tianyu Wang Jun Tang Yuhua Huang Jiaming Gu Yuchan Mai Mingquan Wang Zhishuai Zhang Jiaying Ning Baoqiang Kang Junwei Wang Tiancheng Zhou Yazhou Cui Guangjin Pan |
| author_sort | Fei Li |
| collection | DOAJ |
| description | Abstract Human hematopoiesis starts at early yolk sac and undergoes site- and stage-specific changes over development. The intrinsic mechanism underlying property changes in hematopoiesis ontogeny remains poorly understood. Here, we analyzed single-cell transcriptome of human primary hematopoietic stem/progenitor cells (HSPCs) at different developmental stages, including yolk-sac (YS), AGM, fetal liver (FL), umbilical cord blood (UCB) and adult peripheral blood (PB) mobilized HSPCs. These stage-specific HSPCs display differential intrinsic properties, such as metabolism, self-renewal, differentiating potentialities etc. We then generated highly co-related gene regulatory network (GRNs) modules underlying the differential HSC key properties. Particularly, we identified GRNs and key regulators controlling lymphoid potentiality, self-renewal as well as aerobic respiration in human HSCs. Introducing selected regulators promotes key HSC functions in HSPCs derived from human pluripotent stem cells. Therefore, GRNs underlying key intrinsic properties of human HSCs provide a valuable guide to generate fully functional HSCs in vitro. |
| first_indexed | 2024-04-24T07:15:13Z |
| format | Article |
| id | doaj.art-6fd29a7879b54401a05389d64d7d3a0f |
| institution | Directory Open Access Journal |
| issn | 2045-9769 |
| language | English |
| last_indexed | 2024-04-24T07:15:13Z |
| publishDate | 2024-04-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Cell Regeneration |
| spelling | doaj.art-6fd29a7879b54401a05389d64d7d3a0f2024-04-21T11:20:58ZengSpringerOpenCell Regeneration2045-97692024-04-0113111810.1186/s13619-024-00192-zCharacterization of gene regulatory networks underlying key properties in human hematopoietic stem cell ontogenyFei Li0Yanling Zhu1Tianyu Wang2Jun Tang3Yuhua Huang4Jiaming Gu5Yuchan Mai6Mingquan Wang7Zhishuai Zhang8Jiaying Ning9Baoqiang Kang10Junwei Wang11Tiancheng Zhou12Yazhou Cui13Guangjin Pan14Key Laboratory of Immune Response and Immunotherapy, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences; Guangzhou Medical UniversityKey Laboratory of Immune Response and Immunotherapy, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences; Guangzhou Medical UniversityKey Laboratory of Immune Response and Immunotherapy, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences; Guangzhou Medical UniversityKey Laboratory of Immune Response and Immunotherapy, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences; Guangzhou Medical UniversityKey Laboratory of Immune Response and Immunotherapy, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences; Guangzhou Medical UniversityKey Laboratory of Immune Response and Immunotherapy, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences; Guangzhou Medical UniversityKey Laboratory of Immune Response and Immunotherapy, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences; Guangzhou Medical UniversityKey Laboratory of Immune Response and Immunotherapy, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences; Guangzhou Medical UniversityKey Laboratory of Immune Response and Immunotherapy, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences; Guangzhou Medical UniversityKey Laboratory of Immune Response and Immunotherapy, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences; Guangzhou Medical UniversityKey Laboratory of Immune Response and Immunotherapy, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences; Guangzhou Medical UniversityKey Laboratory of Immune Response and Immunotherapy, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences; Guangzhou Medical UniversityKey Laboratory of Immune Response and Immunotherapy, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences; Guangzhou Medical UniversityKey Lab for Rare & Uncommon Diseases of Shandong Province, Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Shandong First Medical University & Shandong Academy of Medical SciencesKey Laboratory of Immune Response and Immunotherapy, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences; Guangzhou Medical UniversityAbstract Human hematopoiesis starts at early yolk sac and undergoes site- and stage-specific changes over development. The intrinsic mechanism underlying property changes in hematopoiesis ontogeny remains poorly understood. Here, we analyzed single-cell transcriptome of human primary hematopoietic stem/progenitor cells (HSPCs) at different developmental stages, including yolk-sac (YS), AGM, fetal liver (FL), umbilical cord blood (UCB) and adult peripheral blood (PB) mobilized HSPCs. These stage-specific HSPCs display differential intrinsic properties, such as metabolism, self-renewal, differentiating potentialities etc. We then generated highly co-related gene regulatory network (GRNs) modules underlying the differential HSC key properties. Particularly, we identified GRNs and key regulators controlling lymphoid potentiality, self-renewal as well as aerobic respiration in human HSCs. Introducing selected regulators promotes key HSC functions in HSPCs derived from human pluripotent stem cells. Therefore, GRNs underlying key intrinsic properties of human HSCs provide a valuable guide to generate fully functional HSCs in vitro.https://doi.org/10.1186/s13619-024-00192-zHematopoietic stem cellTranscription factorsLineage potentialGene regulatory networksHuman induced pluripotent stem cellsHematopoietic differentiation |
| spellingShingle | Fei Li Yanling Zhu Tianyu Wang Jun Tang Yuhua Huang Jiaming Gu Yuchan Mai Mingquan Wang Zhishuai Zhang Jiaying Ning Baoqiang Kang Junwei Wang Tiancheng Zhou Yazhou Cui Guangjin Pan Characterization of gene regulatory networks underlying key properties in human hematopoietic stem cell ontogeny Cell Regeneration Hematopoietic stem cell Transcription factors Lineage potential Gene regulatory networks Human induced pluripotent stem cells Hematopoietic differentiation |
| title | Characterization of gene regulatory networks underlying key properties in human hematopoietic stem cell ontogeny |
| title_full | Characterization of gene regulatory networks underlying key properties in human hematopoietic stem cell ontogeny |
| title_fullStr | Characterization of gene regulatory networks underlying key properties in human hematopoietic stem cell ontogeny |
| title_full_unstemmed | Characterization of gene regulatory networks underlying key properties in human hematopoietic stem cell ontogeny |
| title_short | Characterization of gene regulatory networks underlying key properties in human hematopoietic stem cell ontogeny |
| title_sort | characterization of gene regulatory networks underlying key properties in human hematopoietic stem cell ontogeny |
| topic | Hematopoietic stem cell Transcription factors Lineage potential Gene regulatory networks Human induced pluripotent stem cells Hematopoietic differentiation |
| url | https://doi.org/10.1186/s13619-024-00192-z |
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