Co-Expression of Runx1, Hoxa9, Hlf, and Hoxa7 Confers Multi-Lineage Potential on Hematopoietic Progenitors Derived From Pluripotent Stem Cells
The intrinsic factors that determine the fundamental traits of engraftment ability and multi-lineage potential of hematopoietic stem cells (HSCs) remain elusive. The induction of bona fade HSCs from pluripotent stem cells (PSCs) in dishes is urgently demanded but remains a great challenge in transla...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.859769/full |
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| author | Bo Yu Bingyan Wu Bingyan Wu Pingshan Hong Huan Peng Huan Peng Mengyun Zhang Qi Zhang Qi Zhang Lijuan Liu Lijuan Liu Xiaofei Liu Xiaofei Liu Yang Geng Yang Geng Jinyong Wang Jinyong Wang Yu Lan |
| author_facet | Bo Yu Bingyan Wu Bingyan Wu Pingshan Hong Huan Peng Huan Peng Mengyun Zhang Qi Zhang Qi Zhang Lijuan Liu Lijuan Liu Xiaofei Liu Xiaofei Liu Yang Geng Yang Geng Jinyong Wang Jinyong Wang Yu Lan |
| author_sort | Bo Yu |
| collection | DOAJ |
| description | The intrinsic factors that determine the fundamental traits of engraftment ability and multi-lineage potential of hematopoietic stem cells (HSCs) remain elusive. The induction of bona fade HSCs from pluripotent stem cells (PSCs) in dishes is urgently demanded but remains a great challenge in translational medicine. Runx1, Hoxa9, Hlf, and Hoxa7 are developmentally co-expressed during endothelial-to-hematopoietic transition and adult haematopoiesis. However, the expression of these factors fails to be turned on during in vitro hematopoietic induction from PSCs. Here, we established an inducible gene over-expression embryonic stem cell (ESC) line in which exogenous Runx1, Hoxa9, Hlf, and Hoxa7 genes were tandemly knocked in. A population of induced hematopoietic progenitor cells (iHPCs) expressing Kit and Sca1 surface markers were successfully obtained in vitro from the gene edited-ESC line. Upon transplantation of the Runx1-Hoxa9-Hlf-Hoxa7 ESC-derived iHPCs into irradiated immunodeficient mice, they can dominantly contribute to B cells, low proportions of T cells and myeloid cells. However, Runx1-Hoxa9-Hlf ESC-derived iHPCs only produced B lineage cells with extremely low contributions. Our study unveils that the coordination of Runx1, Hoxa9, Hlf, and Hoxa7 led to generation of the hematopoietic progenitors with the capacity of multi-lineage hematopoietic reconstitution in the immunodeficient recipient mice. |
| first_indexed | 2024-12-12T15:23:17Z |
| format | Article |
| id | doaj.art-966208be5ade4a60bfbaede9a75de32c |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-12T15:23:17Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-966208be5ade4a60bfbaede9a75de32c2022-12-22T00:20:20ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-04-011010.3389/fcell.2022.859769859769Co-Expression of Runx1, Hoxa9, Hlf, and Hoxa7 Confers Multi-Lineage Potential on Hematopoietic Progenitors Derived From Pluripotent Stem CellsBo Yu0Bingyan Wu1Bingyan Wu2Pingshan Hong3Huan Peng4Huan Peng5Mengyun Zhang6Qi Zhang7Qi Zhang8Lijuan Liu9Lijuan Liu10Xiaofei Liu11Xiaofei Liu12Yang Geng13Yang Geng14Jinyong Wang15Jinyong Wang16Yu Lan17Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, ChinaCAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaKey Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, ChinaCAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaGMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, ChinaCAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaCAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaCAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaCAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaCAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaKey Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, ChinaThe intrinsic factors that determine the fundamental traits of engraftment ability and multi-lineage potential of hematopoietic stem cells (HSCs) remain elusive. The induction of bona fade HSCs from pluripotent stem cells (PSCs) in dishes is urgently demanded but remains a great challenge in translational medicine. Runx1, Hoxa9, Hlf, and Hoxa7 are developmentally co-expressed during endothelial-to-hematopoietic transition and adult haematopoiesis. However, the expression of these factors fails to be turned on during in vitro hematopoietic induction from PSCs. Here, we established an inducible gene over-expression embryonic stem cell (ESC) line in which exogenous Runx1, Hoxa9, Hlf, and Hoxa7 genes were tandemly knocked in. A population of induced hematopoietic progenitor cells (iHPCs) expressing Kit and Sca1 surface markers were successfully obtained in vitro from the gene edited-ESC line. Upon transplantation of the Runx1-Hoxa9-Hlf-Hoxa7 ESC-derived iHPCs into irradiated immunodeficient mice, they can dominantly contribute to B cells, low proportions of T cells and myeloid cells. However, Runx1-Hoxa9-Hlf ESC-derived iHPCs only produced B lineage cells with extremely low contributions. Our study unveils that the coordination of Runx1, Hoxa9, Hlf, and Hoxa7 led to generation of the hematopoietic progenitors with the capacity of multi-lineage hematopoietic reconstitution in the immunodeficient recipient mice.https://www.frontiersin.org/articles/10.3389/fcell.2022.859769/fullRunx1Hoxa9HlfHoxa7pluripotent stem cellstranscription factors |
| spellingShingle | Bo Yu Bingyan Wu Bingyan Wu Pingshan Hong Huan Peng Huan Peng Mengyun Zhang Qi Zhang Qi Zhang Lijuan Liu Lijuan Liu Xiaofei Liu Xiaofei Liu Yang Geng Yang Geng Jinyong Wang Jinyong Wang Yu Lan Co-Expression of Runx1, Hoxa9, Hlf, and Hoxa7 Confers Multi-Lineage Potential on Hematopoietic Progenitors Derived From Pluripotent Stem Cells Frontiers in Cell and Developmental Biology Runx1 Hoxa9 Hlf Hoxa7 pluripotent stem cells transcription factors |
| title | Co-Expression of Runx1, Hoxa9, Hlf, and Hoxa7 Confers Multi-Lineage Potential on Hematopoietic Progenitors Derived From Pluripotent Stem Cells |
| title_full | Co-Expression of Runx1, Hoxa9, Hlf, and Hoxa7 Confers Multi-Lineage Potential on Hematopoietic Progenitors Derived From Pluripotent Stem Cells |
| title_fullStr | Co-Expression of Runx1, Hoxa9, Hlf, and Hoxa7 Confers Multi-Lineage Potential on Hematopoietic Progenitors Derived From Pluripotent Stem Cells |
| title_full_unstemmed | Co-Expression of Runx1, Hoxa9, Hlf, and Hoxa7 Confers Multi-Lineage Potential on Hematopoietic Progenitors Derived From Pluripotent Stem Cells |
| title_short | Co-Expression of Runx1, Hoxa9, Hlf, and Hoxa7 Confers Multi-Lineage Potential on Hematopoietic Progenitors Derived From Pluripotent Stem Cells |
| title_sort | co expression of runx1 hoxa9 hlf and hoxa7 confers multi lineage potential on hematopoietic progenitors derived from pluripotent stem cells |
| topic | Runx1 Hoxa9 Hlf Hoxa7 pluripotent stem cells transcription factors |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2022.859769/full |
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