Lineage infidelity in myeloid cells with TCR gene rearrangement: A latent developmental potential of proT cells revealed by ectopic cytokine receptor signaling
Open accessAbstract
The most immature lymphoid-committed progenitors in both the bone marrow (common lymphoid progenitor) and thymus (proT1) maintain a latent granulocyte/macrophage (G/M) differentiation potential that can be initiated by signals emanating from exogenously expressed IL-2 receptors. In this study, we investigate at which developmental stage thymocytes lose this G/M differentiation potential. We demonstrate that the next maturational stage after proT1 cells (proT2), but not preT (TN3) cells, can convert cell fate from lymphoid to myeloid in response to ectopic IL-2 receptor signaling in human IL-2Rbeta transgenic mice. It is significant that approximately 10% of clonogenic G/M colonies derived from proT cells of IL-2Rbeta transgenic mice have DJ rearrangement specifically at the Dbeta1 but not Dbeta2 segment in the TCRbeta locus. No TCR gene rearrangement is observed in G/M cells from nontransgenic mice, suggesting that the G/M cells we observe in this system were truly lymphoid-committed before stimulation with IL-2. In addition, Dbeta1 and Dbeta2 DJ rearrangement of the TCRbeta gene may be differentially regulated and thus serve as markers for distinct proT cell maturational stages.
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ETP and DN2 cells can generate myeloid cells if removed from the thymus, whereas pro-T cells past PU.1 expression (DN3 or later) do not make myeloid cells under these conditions.
“Whereas ETP and DN2 cells can generate myeloid cells if removed from the thymus, pro-T cells that have differentiated past the stage of PU.1 expression in the thymus (i.e., from the DN2 stage to the DN3 stage or later) do not make myeloid cells under these conditions”
From Mechanisms of Action of Hematopoietic Transcription Factor PU.1 in Initiation of T-Cell Development (2019) · cites this paper as [53]
The Results (page not specified) show that isolated proT1 and proT2 cells generated granulocyte/macrophage cells, whereas TN3 and TN4 cells did not, in the tested cultures. But proT2 myeloid development required ectopic IL-2 receptor expression and added human IL-2; removal from the thymus alone was not sufficient. The cited passages also do not establish PU.1 expression as the reason for the DN2-to-DN3 boundary. (LLM, conf=0.88)
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- Authors
- King, A. G., Kondo, M., Scherer, D. C., & Weissman, I. L.
- Affiliations
- Duke Medical Center (US)
- Corresponding author
- Kondo, Motonari
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2002-03-26
- Volume
- 99
- Issue
- 7
- Pages
- 4508-4513
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC123678
- OpenAlex
- W2154577970
- Cited by
- 115
- References
- 2
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2021: 1 · 2020: 1 · 2019: 3 · 2018: 4 · 2017: 1 · 2016: 3 · 2015: 2 · 2014: 4 · 2013: 1 · 2012: 2
- FWCI
- 4.61
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Cancer Society
- National Institutes of Health (5r35ca042551-13)
- U.S. Public Health Service
- National Cancer Institute (CA09302, CA 42551, T32CA009302)
- National Institute of Allergy and Infectious Diseases (R21AI047458, AI47457, AI47458, R01AI047458, R01AI047457)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- lineage infidelity, myeloid cells, T cell development, TCR beta gene rearrangement, IL-2 receptor signaling, common lymphoid progenitors
- MeSH terms
- Animals, Cell Differentiation, Cells, Cultured, Hematopoietic Stem Cells, Interleukin-2, Mice, Inbred C57BL, Mice, Transgenic, T-Lymphocytes, Gene Rearrangement, T-Lymphocyte, Receptors, Interleukin-2, Cell Lineage, Mice
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