FOXO Dictates Initiation of B Cell Development and Myeloid Restriction in Common Lymphoid Progenitors
The development of B cells relies on an intricate network of transcription factors critical for developmental progression and lineage commitment. In the B cell developmental trajectory, a temporal switch from predominant Foxo3 to Foxo1 expression occurs at the CLP stage. Utilizing VAV-iCre mediated...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.880668/full |
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| author | Lucía Peña-Pérez Lucía Peña-Pérez Shabnam Kharazi Shabnam Kharazi Nicolai Frengen Nicolai Frengen Aleksandra Krstic Aleksandra Krstic Thibault Bouderlique Thibault Bouderlique Julia Hauenstein Julia Hauenstein Minghui He Ece Somuncular Ece Somuncular Xiaoze Li Wang Xiaoze Li Wang Carin Dahlberg Charlotte Gustafsson Charlotte Gustafsson Ann-Sofie Johansson Ann-Sofie Johansson Julian Walfridsson Julian Walfridsson Nadir Kadri Petter Woll Petter Woll Marcin Kierczak Hong Qian Hong Qian Lisa Westerberg Sidinh Luc Sidinh Luc Robert Månsson Robert Månsson Robert Månsson |
| author_facet | Lucía Peña-Pérez Lucía Peña-Pérez Shabnam Kharazi Shabnam Kharazi Nicolai Frengen Nicolai Frengen Aleksandra Krstic Aleksandra Krstic Thibault Bouderlique Thibault Bouderlique Julia Hauenstein Julia Hauenstein Minghui He Ece Somuncular Ece Somuncular Xiaoze Li Wang Xiaoze Li Wang Carin Dahlberg Charlotte Gustafsson Charlotte Gustafsson Ann-Sofie Johansson Ann-Sofie Johansson Julian Walfridsson Julian Walfridsson Nadir Kadri Petter Woll Petter Woll Marcin Kierczak Hong Qian Hong Qian Lisa Westerberg Sidinh Luc Sidinh Luc Robert Månsson Robert Månsson Robert Månsson |
| author_sort | Lucía Peña-Pérez |
| collection | DOAJ |
| description | The development of B cells relies on an intricate network of transcription factors critical for developmental progression and lineage commitment. In the B cell developmental trajectory, a temporal switch from predominant Foxo3 to Foxo1 expression occurs at the CLP stage. Utilizing VAV-iCre mediated conditional deletion, we found that the loss of FOXO3 impaired B cell development from LMPP down to B cell precursors, while the loss of FOXO1 impaired B cell commitment and resulted in a complete developmental block at the CD25 negative proB cell stage. Strikingly, the combined loss of FOXO1 and FOXO3 resulted in the failure to restrict the myeloid potential of CLPs and the complete loss of the B cell lineage. This is underpinned by the failure to enforce the early B-lineage gene regulatory circuitry upon a predominantly pre-established open chromatin landscape. Altogether, this demonstrates that FOXO3 and FOXO1 cooperatively govern early lineage restriction and initiation of B-lineage commitment in CLPs. |
| first_indexed | 2024-12-11T22:04:36Z |
| format | Article |
| id | doaj.art-8607115034c64df893cbadd484c41780 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T22:04:36Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-8607115034c64df893cbadd484c417802022-12-22T00:48:59ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-05-011310.3389/fimmu.2022.880668880668FOXO Dictates Initiation of B Cell Development and Myeloid Restriction in Common Lymphoid ProgenitorsLucía Peña-Pérez0Lucía Peña-Pérez1Shabnam Kharazi2Shabnam Kharazi3Nicolai Frengen4Nicolai Frengen5Aleksandra Krstic6Aleksandra Krstic7Thibault Bouderlique8Thibault Bouderlique9Julia Hauenstein10Julia Hauenstein11Minghui He12Ece Somuncular13Ece Somuncular14Xiaoze Li Wang15Xiaoze Li Wang16Carin Dahlberg17Charlotte Gustafsson18Charlotte Gustafsson19Ann-Sofie Johansson20Ann-Sofie Johansson21Julian Walfridsson22Julian Walfridsson23Nadir Kadri24Petter Woll25Petter Woll26Marcin Kierczak27Hong Qian28Hong Qian29Lisa Westerberg30Sidinh Luc31Sidinh Luc32Robert Månsson33Robert Månsson34Robert Månsson35Center for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, SwedenDepartment of Laboratory Medicine, Karolinska Institutet, Stockholm, SwedenCenter for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, SwedenDepartment of Laboratory Medicine, Karolinska Institutet, Stockholm, SwedenCenter for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, SwedenDepartment of Laboratory Medicine, Karolinska Institutet, Stockholm, SwedenCenter for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, SwedenDepartment of Laboratory Medicine, Karolinska Institutet, Stockholm, SwedenCenter for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, SwedenDepartment of Laboratory Medicine, Karolinska Institutet, Stockholm, SwedenCenter for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, SwedenDepartment of Laboratory Medicine, Karolinska Institutet, Stockholm, SwedenDepartment of Microbiology Tumor and Cell Biology, Karolinska Institutet, Stockholm, SwedenCenter for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, SwedenDepartment of Medicine, Huddinge, Karolinska Institutet, Stockholm, SwedenCenter for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, SwedenDepartment of Laboratory Medicine, Karolinska Institutet, Stockholm, SwedenDepartment of Microbiology Tumor and Cell Biology, Karolinska Institutet, Stockholm, SwedenCenter for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, SwedenDepartment of Laboratory Medicine, Karolinska Institutet, Stockholm, SwedenCenter for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, SwedenDepartment of Medicine, Huddinge, Karolinska Institutet, Stockholm, SwedenCenter for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, SwedenDepartment of Medicine, Huddinge, Karolinska Institutet, Stockholm, SwedenDepartment of Medicine, Solna, Karolinska Institutet, Stockholm, SwedenCenter for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, SwedenDepartment of Medicine, Huddinge, Karolinska Institutet, Stockholm, SwedenDepartment of Cell and Molecular Biology, National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Uppsala University, Uppsala, SwedenCenter for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, SwedenDepartment of Medicine, Huddinge, Karolinska Institutet, Stockholm, SwedenDepartment of Microbiology Tumor and Cell Biology, Karolinska Institutet, Stockholm, SwedenCenter for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, SwedenDepartment of Medicine, Huddinge, Karolinska Institutet, Stockholm, SwedenCenter for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, SwedenDepartment of Laboratory Medicine, Karolinska Institutet, Stockholm, SwedenHematology Center, Karolinska University Hospital, Stockholm, SwedenThe development of B cells relies on an intricate network of transcription factors critical for developmental progression and lineage commitment. In the B cell developmental trajectory, a temporal switch from predominant Foxo3 to Foxo1 expression occurs at the CLP stage. Utilizing VAV-iCre mediated conditional deletion, we found that the loss of FOXO3 impaired B cell development from LMPP down to B cell precursors, while the loss of FOXO1 impaired B cell commitment and resulted in a complete developmental block at the CD25 negative proB cell stage. Strikingly, the combined loss of FOXO1 and FOXO3 resulted in the failure to restrict the myeloid potential of CLPs and the complete loss of the B cell lineage. This is underpinned by the failure to enforce the early B-lineage gene regulatory circuitry upon a predominantly pre-established open chromatin landscape. Altogether, this demonstrates that FOXO3 and FOXO1 cooperatively govern early lineage restriction and initiation of B-lineage commitment in CLPs.https://www.frontiersin.org/articles/10.3389/fimmu.2022.880668/fullB cellFOXO (forkhead box protein O)lineage commitment/specificationmyeloid restrictiongene regulation |
| spellingShingle | Lucía Peña-Pérez Lucía Peña-Pérez Shabnam Kharazi Shabnam Kharazi Nicolai Frengen Nicolai Frengen Aleksandra Krstic Aleksandra Krstic Thibault Bouderlique Thibault Bouderlique Julia Hauenstein Julia Hauenstein Minghui He Ece Somuncular Ece Somuncular Xiaoze Li Wang Xiaoze Li Wang Carin Dahlberg Charlotte Gustafsson Charlotte Gustafsson Ann-Sofie Johansson Ann-Sofie Johansson Julian Walfridsson Julian Walfridsson Nadir Kadri Petter Woll Petter Woll Marcin Kierczak Hong Qian Hong Qian Lisa Westerberg Sidinh Luc Sidinh Luc Robert Månsson Robert Månsson Robert Månsson FOXO Dictates Initiation of B Cell Development and Myeloid Restriction in Common Lymphoid Progenitors Frontiers in Immunology B cell FOXO (forkhead box protein O) lineage commitment/specification myeloid restriction gene regulation |
| title | FOXO Dictates Initiation of B Cell Development and Myeloid Restriction in Common Lymphoid Progenitors |
| title_full | FOXO Dictates Initiation of B Cell Development and Myeloid Restriction in Common Lymphoid Progenitors |
| title_fullStr | FOXO Dictates Initiation of B Cell Development and Myeloid Restriction in Common Lymphoid Progenitors |
| title_full_unstemmed | FOXO Dictates Initiation of B Cell Development and Myeloid Restriction in Common Lymphoid Progenitors |
| title_short | FOXO Dictates Initiation of B Cell Development and Myeloid Restriction in Common Lymphoid Progenitors |
| title_sort | foxo dictates initiation of b cell development and myeloid restriction in common lymphoid progenitors |
| topic | B cell FOXO (forkhead box protein O) lineage commitment/specification myeloid restriction gene regulation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.880668/full |
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