T/B lineage choice occurs prior to intrathymic Notch signaling
Abstract
Commitment of hemopoietic progenitors to the T-cell lineage is a crucial requirement for T-cell development, yet the timing and developmental cues regulating this process remain controversial. Here we have devised a technique to analyze the T-cell/B-cell lineage potential of precursors that have been recruited to the fetal mouse thymus but which have yet to contact the thymic epithelial microenvironment. We show that lymphoid progenitors arriving at the thymus are not bipotent T/B precursors, and provide evidence that intrathymic Notch signaling is not the mechanism determining T/B lineage choice in migrant precursors. Rather, we provide evidence that Notch signaling influences T/B lineage choice in lymphoid precursors through interactions with defined stromal components within the fetal liver. Collectively, our data redefine our understanding of the role and timing of Notch signaling in relation to lineage choices in lymphoid precursors.
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This difference is now understood to be intrinsically programmed and due to an altered pathway of differentiation in the first-wave cells, which results in T-cell lineage commitment even before entry into the thymus.
“This is now understood to be intrinsically programmed (136) and due to an altered pathway of differentiation in the first-wave cells, which results in T-cell lineage commitment even before entry into the thymus (137–139).”
From Mechanisms of Action of Hematopoietic Transcription Factor PU.1 in Initiation of T-Cell Development (2019) · cites this paper as [137]
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Rothenberg, E. V. (2024) · Elsevier eBooks · doi:10.1016/b978-0-128-24465-4.00018-1
Control of early human lymphoid development
Schotte, R. (2007) · Data Archiving and Networked Services (DANS)
Miri-Nezhad, A. (2013) · theses.fr (ABES) · doi:10.70675/a7321c69z76d9z4e51z831dzd5ff75041fbd
- Authors
- Harman, B. C., Jenkinson, W. E., Parnell, S. M., Rossi, S. W., Jenkinson, E. J., & Anderson, G.
- Affiliations
- University of Birmingham (GB)
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2005-08-01
- Volume
- 106
- Issue
- 3
- Pages
- 886-892
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2007923700
- Cited by
- 80
- References
- 25
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 1 · 2022: 1 · 2019: 1 · 2018: 2 · 2016: 6 · 2015: 3 · 2014: 1 · 2013: 3 · 2012: 6
- FWCI
- 4.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- 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
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- T cell lineage commitment, B cell lineage commitment, Notch signaling, thymus, thymic stromal cells, fetal liver, lymphoid progenitors, T cell development, hematopoietic progenitor differentiation
- MeSH terms
- Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases, Animals, B-Lymphocytes, Cell Communication, Epithelial Cells, Fetus, Liver, Membrane Proteins, Mice, Inbred BALB C, Phosphoric Monoester Hydrolases, T-Lymphocytes, Thymus Gland, Stromal Cells, Mice, Knockout, Coculture Techniques, Cell Lineage, Mice, Receptors, Notch
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