The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
Notch/Delta signaling constrains reengineering of pro-T cells by PU.1
Open accessAbstract
PU.1 is essential for early stages of mouse T cell development but antagonizes it if expressed constitutively. Two separable mechanisms are involved: attenuation and diversion. Dysregulated PU.1 expression inhibits pro-T cell survival, proliferation, and passage through β-selection by blocking essential T cell transcription factors, signaling molecules, and Rag gene expression, which expression of a rearranged T cell antigen receptor transgene cannot rescue. However, Bcl2 transgenic cells are protected from this attenuation and may even undergo β-selection, as shown by PU.1 transduction of defined subsets of Bcl2 transgenic fetal thymocytes with differentiation in OP9-DL1 and OP9 control cultures. The outcome of PU.1 expression in these cells depends on Notch/Delta signaling. PU.1 can efficiently divert thymocytes toward a myeloid-like state with multigene regulatory changes, but Notch/Delta signaling vetoes diversion. Gene expression analysis distinguishes sets of critical T lineage regulatory genes with different combinatorial responses to PU.1 and Notch/Delta signals, suggesting particular importance for inhibition of E proteins, Myb, and/or Gfi1 (growth factor independence 1) in diversion. However, Notch signaling only protects against diversion of cells that have undergone T lineage specification after Thy-1 and CD25 up-regulation. The results imply that in T cell precursors, Notch/Delta signaling normally acts to modulate and channel PU.1 transcriptional activities during the stages from T lineage specification until commitment.
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“In primary pro-T cells and Scid.adh.2C2 cells, highly overexpressed PU.1 appears to inhibit Notch signaling, as measured by downregulation of Notch target genes and even Notch1 itself.”
From Mechanisms of Action of Hematopoietic Transcription Factor PU.1 in Initiation of T-Cell Development (2019) · cites this paper as [49]
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“Even artificially high-level PU.1 could only redirect the differentiation of the cells to myeloid or dendritic fates if Notch signaling were reduced (49, 50, 58).”
From Mechanisms of Action of Hematopoietic Transcription Factor PU.1 in Initiation of T-Cell Development (2019) · cites this paper as [49]
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In the citing paper
“re-expression of PU.1 after T-cell commitment turns on myeloid genes and readily transforms later pro-T cells into dendritic cells, macrophages, or promyelocytic-like cells (46–50).”
From Mechanisms of Action of Hematopoietic Transcription Factor PU.1 in Initiation of T-Cell Development (2019) · cites this paper as [49]
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“PU.1 actions are Notch-sensitive.”
From Mechanisms of Action of Hematopoietic Transcription Factor PU.1 in Initiation of T-Cell Development (2019) · cites this paper as [49]
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“it strongly inhibits the proliferation of pro-T cells under conditions that do not reward the cells for lineage switching (49).”
From Mechanisms of Action of Hematopoietic Transcription Factor PU.1 in Initiation of T-Cell Development (2019) · cites this paper as [49]
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Citations
Cites
Induction of T Cell Development from Hematopoietic Progenitor Cells by Delta-like-1 In Vitro
Schmitt, T. M., & Zúñiga-Pflücker, J. C. (2002) · Immunity · doi:10.1016/s1074-7613(02)00474-0 · Cited by 1,120
Stepwise Reprogramming of B Cells into Macrophages
Xie, H., Ye, M., Feng, R., & Graf, T. (2004) · Cell · doi:10.1016/s0092-8674(04)00419-2 · Cited by 987
Transcriptional profiling identifies Id2 function in dendritic cell development
Hacker, C., Kirsch, R. D., Ju, X., Hieronymus, T., Gust, T. C., Kuhl, C., Jorgas, T., Kurz, S. M., Rose‐John, S., Yokota, Y., et al. (2003) · Nature Immunology · doi:10.1038/ni903 · Cited by 544
Transcriptional Control of Early B Cell Development
Busslinger, M. (2004) · Annual Review of Immunology · doi:10.1146/annurev.immunol.22.012703.104807 · Cited by 507
Iwasaki, H., Somoza, C., Shigematsu, H., Duprez, E. A., Iwasaki-Arai, J., Mizuno, S.-I., Arinobu, Y., Geary, K., Zhang, P., Dayaram, T., et al. (2005) · Blood · doi:10.1182/blood-2005-03-0860 · Cited by 433
Schmitt, T. M., Ciofani, M., Petrie, H. T., & Zúñiga‐Pflücker, J. C. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20040394 · Cited by 328
Taghon, T., Yui, M. A., Pant, R., Diamond, R. A., & Rothenberg, E. V. (2006) · Immunity · doi:10.1016/j.immuni.2005.11.012 · Cited by 312
Self-citationPU.1 regulates the commitment of adult hematopoietic progenitors and restricts granulopoiesis
Dakic, A., Metcalf, D., Di Rago, L., Mifsud, S., Wu, L., & Nutt, S. L. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20050075 · Cited by 297
Kee, B. L., & Murre, C. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.188.4.699 · Cited by 267
DETERMINANTS OF LYMPHOID-MYELOID LINEAGE DIVERSIFICATION
Laiosa, C. V., Stadtfeld, M., & Graf, T. (2006) · Annual Review of Immunology · doi:10.1146/annurev.immunol.24.021605.090742 · Cited by 265
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Transcriptional Regulation of T Cell Lineage Commitment
Rothenberg, E. V. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-374279-7.04006-6
Self-citationand denotes lymphopoietic potential
Shimazu, T., Iida, R., Zhang, Q., Welner, R. S., Medina, K. L., Alberola‐Ila, J., & Kincade, P. W. (2016)
An investigation of the role of TRIB2 in steady state and stressed haematopoiesis
Liang, K. L. (2016) · Arrow@dit (Dublin Institute of Technology)
O’Neil, J., & Look, A. T. (2019) · CRC Press eBooks · doi:10.1201/9780429114670-22
Transcriptional Regulation of T-Cell Lineage Commitment
Rothenberg, E. V. (2024) · Elsevier eBooks · doi:10.1016/b978-0-128-24465-4.00018-1
Self-citationDétection des anomalies génétiques dans les LAL-T : de la biologie à la clinique
Abdelali, R. B. (2011) · theses.fr (ABES) · doi:10.70675/90f2a16fz3cdez41f5z8dfez0848b91eb777
Upregulation of CD90 correlates with T lineage commitment at the DN2a stage of T cell development
Parikh, D., Gu, K., Tomei, S., Weber, T. S., Naik, S. H., & Chong, M. M. W. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1940310
Schwarz, B. A., & Bhandoola, A. (2009) · Springer eBooks · doi:10.1007/978-0-387-85816-6_7
Metadata
- Authors
- Franco, C. B., Scripture-Adams, D. D., Proekt, I., Taghon, T., Weiss, A. H., Yui, M. A., Adams, S. L., Diamond, R. A., & Rothenberg, E. V.
- Affiliations
- California Institute of Technology (US)
- University of Southern California (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2006-08-08
- Volume
- 103
- Issue
- 32
- Pages
- 11993-11998
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1567686
- OpenAlex
- W2149251213
- Cited by
- 109
- References
- 34
- Citations by year
- 2026: 1 · 2024: 4 · 2023: 2 · 2022: 1 · 2021: 4 · 2020: 5 · 2019: 8 · 2018: 5 · 2017: 3 · 2016: 7 · 2015: 5 · 2014: 3 · 2013: 11 · 2012: 4
- FWCI
- 3.04
- Type
- journal article
- Language
- en
- Update notices
- correction (2006-09-19)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Funders
- California Institute of Technology
- University of Toronto
- U.S. Public Health Service
- National Cancer Institute (R01CA98925, R01CA90233, R01CA090233, R01CA098925)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- PU.1, Delta-Notch signaling, T cell development, pro-T cells, beta-selection, Bcl-2, E protein, MYB, GFI1, transcriptional regulation, thymocytes, RAG genes, T cell receptor
- MeSH terms
- Proto-Oncogene Protein Spi-1, Animals, Cell Survival, Gene Expression Regulation, Mice, Inbred C57BL, Mice, Transgenic, Models, Biological, Proto-Oncogene Proteins, T-Lymphocytes, Receptors, Interleukin-2, Signal Transduction, Trans-Activators, Cell Lineage, Proto-Oncogene Proteins c-bcl-2, Mice, Receptor, Notch1
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