Global transcriptional analysis of primitive thymocytes reveals accelerated dynamics of T cell specification in fetal stages
Open accessAbstract
T cell development constitutes a multistage process allowing the dissection of events resulting in cellular commitment and functional specification in a specialized microenvironment. This process is guided by the appropriate expression of regulatory genetic factors like transcriptional activators or repressors which are, in part, dependent on instructive signals of the microenvironment. To date, it remains unclear whether exactly the same genetic mechanism acts in adult compared to fetal T cell development. In order to directly compare T cell commitment during adult and fetal differentiation, we isolated subsequent stages of intrathymic subpopulations starting with early canonical T cell progenitors up to irreversibly committed T cell precursors. The genome-wide analysis revealed several distinct gene clusters with a specific pattern of gene regulation for each subset. The largest cluster contained genes upregulated after transition through the most primitive pool into the next transitory population with a consistently elevated expression of elements associated with ongoing T cell fate specification, like Gata3 and Tcf7, in fetal progenitors. Furthermore, adult and fetal T cell progenitors occupied distinct "transcriptional territories" revealing a precise land map of the progression to final T cell commitment operating in different developmental windows. The presence and/or elevated expression of elements associated with an ongoing establishment of a T cell signature in the most primitive fetal subset is highly suggestive for an extrathymic initiation of T cell specification and underlines the fundamental differences in fetal versus adult lymphopoiesis.
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Gene expression differences have been noted between normal first-wave fetal and adult pro-T cells in the thymus at corresponding stages which indicate that the fetal program drives accelerated development.
“Gene expression differences have been noted between the normal first-wave fetal and adult pro-T cells in the thymus at corresponding stages which indicate that the fetal program drives accelerated development (148, 149).”
From Mechanisms of Action of Hematopoietic Transcription Factor PU.1 in Initiation of T-Cell Development (2019) · cites this paper as [149]
The Results (Organization of transcriptional territories; page unavailable) report that fetal progenitors at corresponding stages have different gene-expression signatures and are more advanced in T-cell specification than adult progenitors. However, the cells analyzed were from E15.5 fetal thymi; the Results (Phenotypic and proliferative differences; page unavailable) distinguish them from the first wave of thymus-colonizing cells at E12.5. The paper therefore supports accelerated fetal development, but not the claim's specific identification of the compared cells as first-wave cells. (LLM, conf=0.82)
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“Gene expression differences have been noted between the normal first-wave fetal and adult pro-T cells in the thymus at corresponding stages which indicate that the fetal program drives accelerated development (148, 149).”
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- Authors
- Belyaev, N. N., Biró, J., Athanasakis, D., Fernandez-Reyes, D., & Potocnik, A. J.
- Affiliations
- National Institute for Medical Research (GB)
- Corresponding author
- Potocnik, Alexandre J.
- Venue
- Immunogenetics
- Published
- 2012-05-13
- Volume
- 64
- Issue
- 8
- Pages
- 591-604
- ISSN
- 0093-7711 (ISSN-L)
- 1432-1211
- PMC
- PMC3395349
- OpenAlex
- W2055448986
- Cited by
- 24
- References
- 53
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 4 · 2022: 1 · 2021: 3 · 2019: 3 · 2018: 2 · 2017: 1 · 2016: 2 · 2014: 2 · 2013: 3
- FWCI
- 0.70
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Immunogenetics (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- 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
- T cell development, thymocytes, transcriptional regulation, GATA3, TCF1, lymphocyte development, gene expression profiling
- MeSH terms
- Animals, Cell Differentiation, Female, Fetus, Gene Expression Regulation, Hematopoietic Stem Cells, Mice, Inbred C57BL, T-Lymphocytes, Cell Lineage, Gene Expression Profiling, Lymphopoiesis, Microarray Analysis, Mice, Thymocytes
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