ThPOK is a critical multifaceted regulator of myeloid lineage development.
Journal
Nature immunology
ISSN: 1529-2916
Titre abrégé: Nat Immunol
Pays: United States
ID NLM: 100941354
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
received:
06
01
2021
accepted:
06
06
2023
medline:
31
7
2023
pubmed:
21
7
2023
entrez:
20
7
2023
Statut:
ppublish
Résumé
The transcription factor ThPOK (encoded by Zbtb7b) is well known for its role as a master regulator of CD4 lineage commitment in the thymus. Here, we report an unexpected and critical role of ThPOK as a multifaceted regulator of myeloid lineage commitment, differentiation and maturation. Using reporter and knockout mouse models combined with single-cell RNA-sequencing, progenitor transfer and colony assays, we show that ThPOK controls monocyte-dendritic cell versus granulocyte lineage production during homeostatic differentiation, and serves as a brake for neutrophil maturation in granulocyte lineage-specified cells through transcriptional regulation of lineage-specific transcription factors and RNA via altered messenger RNA splicing to reprogram intron retention.
Identifiants
pubmed: 37474652
doi: 10.1038/s41590-023-01549-3
pii: 10.1038/s41590-023-01549-3
doi:
Substances chimiques
DNA-Binding Proteins
0
RNA
63231-63-0
Transcription Factors
0
Zbtb7b protein, mouse
0
CD4 Antigens
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1295-1307Subventions
Organisme : NIAID NIH HHS
ID : AI068907
Pays : United States
Organisme : NIAID NIH HHS
ID : AI164333
Pays : United States
Organisme : NIGMS NIH HHS
ID : GM107179
Pays : United States
Organisme : NCI NIH HHS
ID : CA195356
Pays : United States
Organisme : NCI NIH HHS
ID : CA006927
Pays : United States
Organisme : NCI NIH HHS
ID : CA211479
Pays : United States
Organisme : NHLBI NIH HHS
ID : HL122661
Pays : United States
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.
Références
Netherby, C. S. et al. The granulocyte progenitor stage is a key target of IRF8-mediated regulation of myeloid-derived suppressor cell production. J. Immunol. 198, 4129–4139 (2017).
pubmed: 28356386
Yanez, A., Goodridge, H. S., Gozalbo, D. & Gil, M. L. TLRs control hematopoiesis during infection. Eur. J. Immunol. 43, 2526–2533 (2013).
pubmed: 24122753
pmcid: 4152461
Manz, M. G. & Boettcher, S. Emergency granulopoiesis. Nat. Rev. Immunol. 14, 302–314 (2014).
pubmed: 24751955
Yanez, A., Megias, J., O’Connor, J. E., Gozalbo, D. & Gil, M. L. Candida albicans induces selective development of macrophages and monocyte derived dendritic cells by a TLR2 dependent signalling. PLoS ONE 6, e24761 (2011).
pubmed: 21935459
pmcid: 3174213
Basu, S. et al. ‘Emergency’ granulopoiesis in G-CSF-deficient mice in response to Candida albicans infection. Blood 95, 3725–3733 (2000).
pubmed: 10845903
Serbina, N. V., Hohl, T. M., Cherny, M. & Pamer, E. G. Selective expansion of the monocytic lineage directed by bacterial infection. J. Immunol. 183, 1900–1910 (2009).
pubmed: 19596996
Olsson, A. et al. Single-cell analysis of mixed-lineage states leading to a binary cell fate choice. Nature 537, 698–702 (2016).
pubmed: 27580035
pmcid: 5161694
He, X. et al. The zinc finger transcription factor Th-POK regulates CD4 versus CD8 T-cell lineage commitment. Nature 433, 826–833 (2005).
pubmed: 15729333
He, X. et al. CD4-CD8 lineage commitment is regulated by a silencer element at the ThPOK transcription-factor locus. Immunity 28, 346–358 (2008).
pubmed: 18342007
Park, K. et al. TCR-mediated ThPOK induction promotes development of mature (CD24
pubmed: 20551904
pmcid: 2910264
Engel, I., Zhao, M., Kappes, D., Taniuchi, I. & Kronenberg, M. The transcription factor Th-POK negatively regulates Th17 differentiation in Vα14i NKT cells. Blood 120, 4524–4532 (2012).
pubmed: 23034280
pmcid: 3512232
Lee, H. O. et al. Disregulated expression of the transcription factor ThPOK during T-cell development leads to high incidence of T-cell lymphomas. Proc. Natl Acad. Sci. USA 112, 7773–7778 (2015).
pubmed: 26056302
pmcid: 4485124
Evrard, M. et al. Developmental analysis of bone marrow neutrophils reveals populations specialized in expansion, trafficking, and effector functions. Immunity 48, 364–379 (2018).
pubmed: 29466759
Xie, X. et al. Single-cell transcriptome profiling reveals neutrophil heterogeneity in homeostasis and infection. Nat. Immunol. 21, 1119–1133 (2020).
pubmed: 32719519
pmcid: 7442692
Blazek, K. et al. IFN-λ resolves inflammation via suppression of neutrophil infiltration and IL-1β production. J. Exp. Med. 212, 845–853 (2015).
pubmed: 25941255
pmcid: 4451128
Shrum, B. et al. A robust scoring system to evaluate sepsis severity in an animal model. BMC Res. Notes 7, 233 (2014).
pubmed: 24725742
pmcid: 4022086
Muench, D. E. et al. Mouse models of neutropenia reveal progenitor-stage-specific defects. Nature 582, 109–114 (2020).
pubmed: 32494068
pmcid: 8041154
Kwok, I. et al. Combinatorial single-cell analyses of granulocyte-monocyte progenitor heterogeneity reveals an early uni-potent neutrophil progenitor. Immunity 53, 303–318.e5 (2020).
pubmed: 32579887
Amir el, A. D. et al. viSNE enables visualization of high dimensional single-cell data and reveals phenotypic heterogeneity of leukemia. Nat. Biotechnol. 31, 545–552 (2013).
Yamamoto, R. et al. Clonal analysis unveils self-renewing lineage-restricted progenitors generated directly from hematopoietic stem cells. Cell 154, 1112–1126 (2013).
pubmed: 23993099
DePasquale, E. A. K. et al. cellHarmony: cell-level matching and holistic comparison of single-cell transcriptomes. Nucleic Acids Res. 47, e138 (2019).
pubmed: 31529053
pmcid: 6868361
La Manno, G. et al. RNA velocity of single cells. Nature 560, 494–498 (2018).
pubmed: 30089906
pmcid: 6130801
Nutt, S. L. & Chopin, M. Transcriptional networks driving dendritic cell differentiation and function. Immunity 16, 942 (2020).
Sunami, Y. et al. BCL11A promotes myeloid leukemogenesis by repressing PU.1 target genes. Blood Adv. 6, 1827–1843 (2022).
pubmed: 34714913
pmcid: 8941473
Gruber, T. A. et al. An Inv(16)(p13.3q24.3)-encoded CBFA2T3-GLIS2 fusion protein defines an aggressive subtype of pediatric acute megakaryoblastic leukemia. Cancer Cell 22, 683–697 (2012).
pubmed: 23153540
pmcid: 3547667
Masetti, R., Bertuccio, S. N., Pession, A. & Locatelli, F. CBFA2T3-GLIS2-positive acute myeloid leukaemia. A peculiar paediatric entity. Br. J. Haematol. 184, 337–347 (2019).
pubmed: 30592296
Saha, S. et al. Transcriptomic analysis identifies RNA binding proteins as putative regulators of myelopoiesis and leukemia. Front. Oncol. 9, 692 (2019).
pubmed: 31448224
pmcid: 6691814
Diaz-Munoz, M. D. & Turner, M. Uncovering the role of RNA-binding proteins in gene expression in the immune system. Front. Immunol. 9, 1094 (2018).
pubmed: 29875770
pmcid: 5974052
Wong, J. J. et al. Orchestrated intron retention regulates normal granulocyte differentiation. Cell 154, 583–595 (2013).
pubmed: 23911323
Itskovich, S. S. et al. MBNL1 regulates essential alternative RNA splicing patterns in MLL-rearranged leukemia. Nat. Commun. 11, 2369 (2020).
pubmed: 32398749
pmcid: 7217953
Skoda, R. C. & Schwaller, J. Dual roles of EZH2 in acute myeloid leukemia. J. Exp. Med. 216, 725–727 (2019).
pubmed: 30890555
pmcid: 6446873
Sumter, T. F. et al. The High Mobility Group A1 (HMGA1) transcriptome in cancer and development. Curr. Mol. Med. 16, 353–393 (2016).
pubmed: 26980699
pmcid: 5408585
Iervolino, A. et al. hnRNP A1 nucleocytoplasmic shuttling activity is required for normal myelopoiesis and BCR/ABL leukemogenesis. Mol. Cell. Biol. 22, 2255–2266 (2002).
pubmed: 11884611
pmcid: 133663
Hodson, D. J., Screen, M. & Turner, M. RNA-binding proteins in hematopoiesis and hematological malignancy. Blood 133, 2365–2373 (2019).
pubmed: 30967369
pmcid: 6716123
Basu, J. et al. Essential role of a ThPOK autoregulatory loop in the maintenance of mature CD4
pubmed: 34312548
pmcid: 8887595
Sun, F., Xiao, G. & Qu, Z. Murine bronchoalveolar lavage. Bio Protoc. 7, e2287 (2017).
pubmed: 29082285
pmcid: 5659634
Gonçalves, R. & Mosser, D. M. The isolation and characterization of murine macrophages. Curr. Protoc. Immunol. 111, 14.1.1–14.1.16 (2015).
Venkatasubramanian, M., Chetal, K., Schnell, D. J., Atluri, G. & Salomonis, N. Resolving single-cell heterogeneity from hundreds of thousands of cells through sequential hybrid clustering and NMF. Bioinformatics 36, 3773 (2020).
pubmed: 32207533
pmcid: 7320606
Muench, D. E. et al. SKI controls MDS-associated chronic TGF-β signaling, aberrant splicing, and stem cell fitness. Blood 132, e24–e34 (2018).
pubmed: 30249787
pmcid: 6251005
Muller, P. A. et al. Microbiota modulate sympathetic neurons via a gut-brain circuit. Nature 583, 441–446 (2020).
pubmed: 32641826
pmcid: 7367767
Esterházy, D. et al. Compartmentalized gut lymph node drainage dictates adaptive immune responses. Nature 569, 126–130 (2019).
pubmed: 30988509
pmcid: 6587593