Forward programming of hPSCs to neutrophils using chemically defined media
Abstract Polymorphonuclear neutrophils (PMNs), the most abundant leukocytes circulating in human blood, are pivotal players in the innate immune system. In recent years, PMNs have gained increasing recognition for their significant involvement in the pathogenesis of a wide array of human diseases, i...
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| Format: | Article |
| Language: | English |
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BMC
2025-02-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13287-025-04147-2 |
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| author | Hayley E. Hall Xiaoping Bao Cheng Dong Xiaojun Lance Lian |
| author_facet | Hayley E. Hall Xiaoping Bao Cheng Dong Xiaojun Lance Lian |
| author_sort | Hayley E. Hall |
| collection | DOAJ |
| description | Abstract Polymorphonuclear neutrophils (PMNs), the most abundant leukocytes circulating in human blood, are pivotal players in the innate immune system. In recent years, PMNs have gained increasing recognition for their significant involvement in the pathogenesis of a wide array of human diseases, including sepsis, pulmonary conditions, autoimmune disorders, and various cancers. Due to their terminally differentiated state, PMNs possess a short lifespan and exhibit limited proliferative potential, which makes continuous replenishment from the bone marrow essential for maintaining immune homeostasis. This demand underscores the need for efficient, reliable, and robust methods of PMN production. In this study, we evaluated three forward programming protocols and one directed differentiation protocol aimed at generating PMNs from human pluripotent stem cells (hPSCs). We analyzed not only their differentiation efficiency but also the transcriptomic profiles and functional capabilities of the resulting PMNs. Our findings revealed that both the forward programming method and the directed differentiation approach can successfully generate functional PMNs. Furthermore, by fine-tuning the culture media at various stages during forward programming, we identified an optimal protocol that significantly enhances hematopoietic differentiation potential and promotes the functional maturity of the neutrophils. |
| format | Article |
| id | doaj-art-799b11bf5b56480094ed03dfda02c46f |
| institution | Kabale University |
| issn | 1757-6512 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj-art-799b11bf5b56480094ed03dfda02c46f2025-02-09T12:15:48ZengBMCStem Cell Research & Therapy1757-65122025-02-0116111110.1186/s13287-025-04147-2Forward programming of hPSCs to neutrophils using chemically defined mediaHayley E. Hall0Xiaoping Bao1Cheng Dong2Xiaojun Lance Lian3Department of Biomedical Engineering, The Pennsylvania State UniversityDavidson School of Chemical Engineering, Purdue UniversityDepartment of Biomedical Engineering, The Pennsylvania State UniversityDepartment of Biomedical Engineering, The Pennsylvania State UniversityAbstract Polymorphonuclear neutrophils (PMNs), the most abundant leukocytes circulating in human blood, are pivotal players in the innate immune system. In recent years, PMNs have gained increasing recognition for their significant involvement in the pathogenesis of a wide array of human diseases, including sepsis, pulmonary conditions, autoimmune disorders, and various cancers. Due to their terminally differentiated state, PMNs possess a short lifespan and exhibit limited proliferative potential, which makes continuous replenishment from the bone marrow essential for maintaining immune homeostasis. This demand underscores the need for efficient, reliable, and robust methods of PMN production. In this study, we evaluated three forward programming protocols and one directed differentiation protocol aimed at generating PMNs from human pluripotent stem cells (hPSCs). We analyzed not only their differentiation efficiency but also the transcriptomic profiles and functional capabilities of the resulting PMNs. Our findings revealed that both the forward programming method and the directed differentiation approach can successfully generate functional PMNs. Furthermore, by fine-tuning the culture media at various stages during forward programming, we identified an optimal protocol that significantly enhances hematopoietic differentiation potential and promotes the functional maturity of the neutrophils.https://doi.org/10.1186/s13287-025-04147-2Forward programmingDirected DifferentiationPolymorphonuclear neutrophilsHuman pluripotent stem cellsETV2 |
| spellingShingle | Hayley E. Hall Xiaoping Bao Cheng Dong Xiaojun Lance Lian Forward programming of hPSCs to neutrophils using chemically defined media Stem Cell Research & Therapy Forward programming Directed Differentiation Polymorphonuclear neutrophils Human pluripotent stem cells ETV2 |
| title | Forward programming of hPSCs to neutrophils using chemically defined media |
| title_full | Forward programming of hPSCs to neutrophils using chemically defined media |
| title_fullStr | Forward programming of hPSCs to neutrophils using chemically defined media |
| title_full_unstemmed | Forward programming of hPSCs to neutrophils using chemically defined media |
| title_short | Forward programming of hPSCs to neutrophils using chemically defined media |
| title_sort | forward programming of hpscs to neutrophils using chemically defined media |
| topic | Forward programming Directed Differentiation Polymorphonuclear neutrophils Human pluripotent stem cells ETV2 |
| url | https://doi.org/10.1186/s13287-025-04147-2 |
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