Dissecting the process of human neutrophil lineage determination by using alpha-lipoic acid inducing neutrophil deficiency model
Granulocyte-monocyte progenitors (GMPs) differentiate into both neutrophils and monocytes. Recently, uni-potential neutrophil progenitors have been identified both in mice and humans using an array of surface markers. However, how human GMPs commit to neutrophil progenitors and the regulatory mechan...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-08-01
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| Series: | Redox Biology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231722001641 |
| _version_ | 1811322933228863488 |
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| author | Yong Dong Yimeng Zhang Yongping Zhang Xu Pan Ju Bai Yijin Chen Ya Zhou Zhenyang Lai Qiang Chen Shaoyan Hu Qiongxiu Zhou Yonggang Zhang Feng Ma |
| author_facet | Yong Dong Yimeng Zhang Yongping Zhang Xu Pan Ju Bai Yijin Chen Ya Zhou Zhenyang Lai Qiang Chen Shaoyan Hu Qiongxiu Zhou Yonggang Zhang Feng Ma |
| author_sort | Yong Dong |
| collection | DOAJ |
| description | Granulocyte-monocyte progenitors (GMPs) differentiate into both neutrophils and monocytes. Recently, uni-potential neutrophil progenitors have been identified both in mice and humans using an array of surface markers. However, how human GMPs commit to neutrophil progenitors and the regulatory mechanisms of fate determination remain incompletely understood. In the present study, we established a human neutrophil deficiency model using the small molecule alpha-lipoic acid. Using this neutrophil deficiency model, we determined that the neutrophil progenitor commitment process from CD371+ CD115– GMPs defined by CD34 and CD15 and discovered that critical signals generated by RNA splicing and rRNA biogenesis regulate the process of early commitment for human early neutrophil progenitors derived from CD371+ CD115– GMPs. These processes were elucidated by single-cell RNA sequencing both in vitro and in vivo derived cells. Sequentially, we identified that the transcription factor ELK1 is essential for human neutrophil lineage commitment using the alpha-lipoic acid (ALA)-inducing neutrophil deficiency model. Finally, we also revealed differential roles for long-ELK1 and short-ELK1, balanced by SF3B1, in the commitment process of neutrophil progenitors. Taken together, we discovered a novel function of ALA in regulating neutrophil lineage specification and identified that the SF3B1-ELK axis regulates the commitment of human neutrophil progenitors from CD371+ CD115– GMPs. |
| first_indexed | 2024-04-13T13:44:55Z |
| format | Article |
| id | doaj.art-a10f27d1c20d41c9b90ab1549ec59d42 |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-04-13T13:44:55Z |
| publishDate | 2022-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-a10f27d1c20d41c9b90ab1549ec59d422022-12-22T02:44:31ZengElsevierRedox Biology2213-23172022-08-0154102392Dissecting the process of human neutrophil lineage determination by using alpha-lipoic acid inducing neutrophil deficiency modelYong Dong0Yimeng Zhang1Yongping Zhang2Xu Pan3Ju Bai4Yijin Chen5Ya Zhou6Zhenyang Lai7Qiang Chen8Shaoyan Hu9Qiongxiu Zhou10Yonggang Zhang11Feng Ma12Center for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu, China; Department of Immunology, School of Basic Medical Sciences, Chengdu Medical College, Chengdu, China; Non-coding RNA and Drug Discovery Key Laboratory of Sichuan Province, Chengdu Medical College, Chengdu, China; Corresponding author. Huacai Road 26, Chengdu, China.Center for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu, ChinaDepartment of Hematology and Oncology, Children's Hospital of Soochow University, Suzhou City, ChinaCenter for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu, ChinaCenter for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu, ChinaCenter for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu, ChinaCenter for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu, ChinaSichuan Cord Blood Bank, Chengdu, ChinaCenter for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu, China; Sichuan Cord Blood Bank, Chengdu, ChinaDepartment of Hematology and Oncology, Children's Hospital of Soochow University, Suzhou City, ChinaCenter for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu, ChinaCenter for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu, ChinaCenter for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu, China; Corresponding author. Huacai Road 26, Chengdu, China.Granulocyte-monocyte progenitors (GMPs) differentiate into both neutrophils and monocytes. Recently, uni-potential neutrophil progenitors have been identified both in mice and humans using an array of surface markers. However, how human GMPs commit to neutrophil progenitors and the regulatory mechanisms of fate determination remain incompletely understood. In the present study, we established a human neutrophil deficiency model using the small molecule alpha-lipoic acid. Using this neutrophil deficiency model, we determined that the neutrophil progenitor commitment process from CD371+ CD115– GMPs defined by CD34 and CD15 and discovered that critical signals generated by RNA splicing and rRNA biogenesis regulate the process of early commitment for human early neutrophil progenitors derived from CD371+ CD115– GMPs. These processes were elucidated by single-cell RNA sequencing both in vitro and in vivo derived cells. Sequentially, we identified that the transcription factor ELK1 is essential for human neutrophil lineage commitment using the alpha-lipoic acid (ALA)-inducing neutrophil deficiency model. Finally, we also revealed differential roles for long-ELK1 and short-ELK1, balanced by SF3B1, in the commitment process of neutrophil progenitors. Taken together, we discovered a novel function of ALA in regulating neutrophil lineage specification and identified that the SF3B1-ELK axis regulates the commitment of human neutrophil progenitors from CD371+ CD115– GMPs.http://www.sciencedirect.com/science/article/pii/S2213231722001641Alpha-lipoic acidNeutrophilsMonocytesELK1SF3B1RNA splicing |
| spellingShingle | Yong Dong Yimeng Zhang Yongping Zhang Xu Pan Ju Bai Yijin Chen Ya Zhou Zhenyang Lai Qiang Chen Shaoyan Hu Qiongxiu Zhou Yonggang Zhang Feng Ma Dissecting the process of human neutrophil lineage determination by using alpha-lipoic acid inducing neutrophil deficiency model Redox Biology Alpha-lipoic acid Neutrophils Monocytes ELK1 SF3B1 RNA splicing |
| title | Dissecting the process of human neutrophil lineage determination by using alpha-lipoic acid inducing neutrophil deficiency model |
| title_full | Dissecting the process of human neutrophil lineage determination by using alpha-lipoic acid inducing neutrophil deficiency model |
| title_fullStr | Dissecting the process of human neutrophil lineage determination by using alpha-lipoic acid inducing neutrophil deficiency model |
| title_full_unstemmed | Dissecting the process of human neutrophil lineage determination by using alpha-lipoic acid inducing neutrophil deficiency model |
| title_short | Dissecting the process of human neutrophil lineage determination by using alpha-lipoic acid inducing neutrophil deficiency model |
| title_sort | dissecting the process of human neutrophil lineage determination by using alpha lipoic acid inducing neutrophil deficiency model |
| topic | Alpha-lipoic acid Neutrophils Monocytes ELK1 SF3B1 RNA splicing |
| url | http://www.sciencedirect.com/science/article/pii/S2213231722001641 |
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