Conversion of placental hemogenic endothelial cells to hematopoietic stem and progenitor cells
Abstract Hematopoietic stem and progenitor cells (HSPCs) are critical for the treatment of blood diseases in clinic. However, the limited source of HSPCs severely hinders their clinical application. In the embryo, hematopoietic stem cells (HSCs) arise from hemogenic endothelial (HE) cells lining the...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-01-01
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| Series: | Cell Discovery |
| Online Access: | https://doi.org/10.1038/s41421-024-00760-2 |
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| author | Guixian Liang Shicheng Liu Chunyu Zhou Mengyao Liu Yifan Zhang Dongyuan Ma Lu Wang Jing-Dong J. Han Feng Liu |
| author_facet | Guixian Liang Shicheng Liu Chunyu Zhou Mengyao Liu Yifan Zhang Dongyuan Ma Lu Wang Jing-Dong J. Han Feng Liu |
| author_sort | Guixian Liang |
| collection | DOAJ |
| description | Abstract Hematopoietic stem and progenitor cells (HSPCs) are critical for the treatment of blood diseases in clinic. However, the limited source of HSPCs severely hinders their clinical application. In the embryo, hematopoietic stem cells (HSCs) arise from hemogenic endothelial (HE) cells lining the major arteries in vivo. In this work, by engineering vascular niche endothelial cells (VN-ECs), we generated functional HSPCs in vitro from ECs at various sites, including the aorta-gonad-mesonephros (AGM) region and the placenta. Firstly, we converted mouse embryonic HE cells from the AGM region (aHE) into induced HSPCs (iHSPCs), which have the abilities for multilineage differentiation and self-renewal. Mechanistically, we found that VN-ECs can promote the generation of iHSPCs via secretion of CX3CL1 and IL1A. Next, through VN-EC co-culture, we showed that placental HE (pHE) cells, a type of extra-embryonic HE cells, were successfully converted into iHSPCs (pHE-iHSPCs), which have multilineage differentiation capacity, but exhibit limited self-renewal ability. Furthermore, comparative transcriptome analysis of aHE-iHSPCs and pHE-iHSPCs showed that aHE-iHSPCs highly expressed HSC-specific and self-renewal-related genes. Moreover, experimental validation showed that retinoic acid (RA) treatment promoted the transformation of pHE cells into iHSPCs that have self-renewal ability. Collectively, our results suggested that pHE cells possess the potential to transform into self-renewing iHSPCs through RA treatment, which will facilitate the clinical application of placental endothelial cells in hematopoietic cell generation. |
| format | Article |
| id | doaj-art-12dbb351c3944748b51cec1655f7bc4b |
| institution | Kabale University |
| issn | 2056-5968 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Discovery |
| spelling | doaj-art-12dbb351c3944748b51cec1655f7bc4b2025-02-02T12:08:27ZengNature Publishing GroupCell Discovery2056-59682025-01-0111111210.1038/s41421-024-00760-2Conversion of placental hemogenic endothelial cells to hematopoietic stem and progenitor cellsGuixian Liang0Shicheng Liu1Chunyu Zhou2Mengyao Liu3Yifan Zhang4Dongyuan Ma5Lu Wang6Jing-Dong J. Han7Feng Liu8Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of SciencesKey Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of SciencesPeking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Center for Quantitative Biology (CQB), Peking UniversityState Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeSchool of Life Sciences, Shandong UniversityKey Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of SciencesState Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegePeking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Center for Quantitative Biology (CQB), Peking UniversityKey Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of SciencesAbstract Hematopoietic stem and progenitor cells (HSPCs) are critical for the treatment of blood diseases in clinic. However, the limited source of HSPCs severely hinders their clinical application. In the embryo, hematopoietic stem cells (HSCs) arise from hemogenic endothelial (HE) cells lining the major arteries in vivo. In this work, by engineering vascular niche endothelial cells (VN-ECs), we generated functional HSPCs in vitro from ECs at various sites, including the aorta-gonad-mesonephros (AGM) region and the placenta. Firstly, we converted mouse embryonic HE cells from the AGM region (aHE) into induced HSPCs (iHSPCs), which have the abilities for multilineage differentiation and self-renewal. Mechanistically, we found that VN-ECs can promote the generation of iHSPCs via secretion of CX3CL1 and IL1A. Next, through VN-EC co-culture, we showed that placental HE (pHE) cells, a type of extra-embryonic HE cells, were successfully converted into iHSPCs (pHE-iHSPCs), which have multilineage differentiation capacity, but exhibit limited self-renewal ability. Furthermore, comparative transcriptome analysis of aHE-iHSPCs and pHE-iHSPCs showed that aHE-iHSPCs highly expressed HSC-specific and self-renewal-related genes. Moreover, experimental validation showed that retinoic acid (RA) treatment promoted the transformation of pHE cells into iHSPCs that have self-renewal ability. Collectively, our results suggested that pHE cells possess the potential to transform into self-renewing iHSPCs through RA treatment, which will facilitate the clinical application of placental endothelial cells in hematopoietic cell generation.https://doi.org/10.1038/s41421-024-00760-2 |
| spellingShingle | Guixian Liang Shicheng Liu Chunyu Zhou Mengyao Liu Yifan Zhang Dongyuan Ma Lu Wang Jing-Dong J. Han Feng Liu Conversion of placental hemogenic endothelial cells to hematopoietic stem and progenitor cells Cell Discovery |
| title | Conversion of placental hemogenic endothelial cells to hematopoietic stem and progenitor cells |
| title_full | Conversion of placental hemogenic endothelial cells to hematopoietic stem and progenitor cells |
| title_fullStr | Conversion of placental hemogenic endothelial cells to hematopoietic stem and progenitor cells |
| title_full_unstemmed | Conversion of placental hemogenic endothelial cells to hematopoietic stem and progenitor cells |
| title_short | Conversion of placental hemogenic endothelial cells to hematopoietic stem and progenitor cells |
| title_sort | conversion of placental hemogenic endothelial cells to hematopoietic stem and progenitor cells |
| url | https://doi.org/10.1038/s41421-024-00760-2 |
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