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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9116193/ https://www.ncbi.nlm.nih.gov/pubmed/35603175 http://dx.doi.org/10.3389/fimmu.2022.880668 |
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author | Peña-Pérez, Lucía Kharazi, Shabnam Frengen, Nicolai Krstic, Aleksandra Bouderlique, Thibault Hauenstein, Julia He, Minghui Somuncular, Ece Li Wang, Xiaoze Dahlberg, Carin Gustafsson, Charlotte Johansson, Ann-Sofie Walfridsson, Julian Kadri, Nadir Woll, Petter Kierczak, Marcin Qian, Hong Westerberg, Lisa Luc, Sidinh Månsson, Robert |
author_facet | Peña-Pérez, Lucía Kharazi, Shabnam Frengen, Nicolai Krstic, Aleksandra Bouderlique, Thibault Hauenstein, Julia He, Minghui Somuncular, Ece Li Wang, Xiaoze Dahlberg, Carin Gustafsson, Charlotte Johansson, Ann-Sofie Walfridsson, Julian Kadri, Nadir Woll, Petter Kierczak, Marcin Qian, Hong Westerberg, Lisa Luc, Sidinh Månsson, Robert |
author_sort | Peña-Pérez, Lucía |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-9116193 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-91161932022-05-19 FOXO Dictates Initiation of B Cell Development and Myeloid Restriction in Common Lymphoid Progenitors Peña-Pérez, Lucía Kharazi, Shabnam Frengen, Nicolai Krstic, Aleksandra Bouderlique, Thibault Hauenstein, Julia He, Minghui Somuncular, Ece Li Wang, Xiaoze Dahlberg, Carin Gustafsson, Charlotte Johansson, Ann-Sofie Walfridsson, Julian Kadri, Nadir Woll, Petter Kierczak, Marcin Qian, Hong Westerberg, Lisa Luc, Sidinh Månsson, Robert Front Immunol Immunology 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. Frontiers Media S.A. 2022-05-04 /pmc/articles/PMC9116193/ /pubmed/35603175 http://dx.doi.org/10.3389/fimmu.2022.880668 Text en Copyright © 2022 Peña-Pérez, Kharazi, Frengen, Krstic, Bouderlique, Hauenstein, He, Somuncular, Li Wang, Dahlberg, Gustafsson, Johansson, Walfridsson, Kadri, Woll, Kierczak, Qian, Westerberg, Luc and Månsson https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Peña-Pérez, Lucía Kharazi, Shabnam Frengen, Nicolai Krstic, Aleksandra Bouderlique, Thibault Hauenstein, Julia He, Minghui Somuncular, Ece Li Wang, Xiaoze Dahlberg, Carin Gustafsson, Charlotte Johansson, Ann-Sofie Walfridsson, Julian Kadri, Nadir Woll, Petter Kierczak, Marcin Qian, Hong Westerberg, Lisa Luc, Sidinh Månsson, Robert FOXO Dictates Initiation of B Cell Development and Myeloid Restriction in Common Lymphoid Progenitors |
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 | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9116193/ https://www.ncbi.nlm.nih.gov/pubmed/35603175 http://dx.doi.org/10.3389/fimmu.2022.880668 |
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