Thymic epithelial cell fate and potency in early organogenesis assessed by single cell transcriptional and functional analysis
During development, cortical (c) and medullary (m) thymic epithelial cells (TEC) arise from the third pharyngeal pouch endoderm. Current models suggest that within the thymic primordium most TEC exist in a bipotent/common thymic epithelial progenitor cell (TEPC) state able to generate both cTEC and...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-07-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1202163/full |
| _version_ | 1797772889689161728 |
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| author | Alison Mary Farley An Chengrui Sam Palmer Dong Liu Anastasia I. Kousa Paul Rouse Viktoria Major Joanna Sweetman Jan Morys Andrea Corsinotti Jennifer Nichols Janice Ure Renee McLay Luke Boulter S. Jon Chapman Simon R. Tomlinson C. Clare Blackburn |
| author_facet | Alison Mary Farley An Chengrui Sam Palmer Dong Liu Anastasia I. Kousa Paul Rouse Viktoria Major Joanna Sweetman Jan Morys Andrea Corsinotti Jennifer Nichols Janice Ure Renee McLay Luke Boulter S. Jon Chapman Simon R. Tomlinson C. Clare Blackburn |
| author_sort | Alison Mary Farley |
| collection | DOAJ |
| description | During development, cortical (c) and medullary (m) thymic epithelial cells (TEC) arise from the third pharyngeal pouch endoderm. Current models suggest that within the thymic primordium most TEC exist in a bipotent/common thymic epithelial progenitor cell (TEPC) state able to generate both cTEC and mTEC, at least until embryonic day 12.5 (E12.5) in the mouse. This view, however, is challenged by recent transcriptomics and genetic evidence. We therefore set out to investigate the fate and potency of TEC in the early thymus. Here using single cell (sc) RNAseq we identify a candidate mTEC progenitor population at E12.5, consistent with recent reports. Via lineage-tracing we demonstrate this population as mTEC fate-restricted, validating our bioinformatics prediction. Using potency analyses we also establish that most E11.5 and E12.5 progenitor TEC are cTEC-fated. Finally we show that overnight culture causes most if not all E12.5 cTEC-fated TEPC to acquire functional bipotency, and provide a likely molecular mechanism for this changed differentiation potential. Collectively, our data overturn the widely held view that a common TEPC predominates in the E12.5 thymus, showing instead that sublineage-primed progenitors are present from the earliest stages of thymus organogenesis but that these early fetal TEPC exhibit cell-fate plasticity in response to extrinsic factors. Our data provide a significant advance in the understanding of fetal thymic epithelial development and thus have implications for thymus-related clinical research, in particular research focussed on generating TEC from pluripotent stem cells |
| first_indexed | 2024-03-12T21:58:15Z |
| format | Article |
| id | doaj.art-9f035f9fc89d4b2ebc3e9d35b9da20b5 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-12T21:58:15Z |
| publishDate | 2023-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-9f035f9fc89d4b2ebc3e9d35b9da20b52023-07-25T13:08:41ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-07-011410.3389/fimmu.2023.12021631202163Thymic epithelial cell fate and potency in early organogenesis assessed by single cell transcriptional and functional analysisAlison Mary Farley0An Chengrui1Sam Palmer2Dong Liu3Anastasia I. Kousa4Paul Rouse5Viktoria Major6Joanna Sweetman7Jan Morys8Andrea Corsinotti9Jennifer Nichols10Janice Ure11Renee McLay12Luke Boulter13S. Jon Chapman14Simon R. Tomlinson15C. Clare Blackburn16Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United KingdomCentre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United KingdomMathematical Institute, University of Oxford, Oxford, United KingdomCentre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United KingdomCentre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United KingdomCentre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United KingdomCentre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United KingdomCentre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United KingdomCentre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United KingdomCentre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United KingdomCentre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United KingdomCentre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United KingdomCentre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United KingdomMedical Research Council (MRC) Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United KingdomMathematical Institute, University of Oxford, Oxford, United KingdomCentre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United KingdomCentre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United KingdomDuring development, cortical (c) and medullary (m) thymic epithelial cells (TEC) arise from the third pharyngeal pouch endoderm. Current models suggest that within the thymic primordium most TEC exist in a bipotent/common thymic epithelial progenitor cell (TEPC) state able to generate both cTEC and mTEC, at least until embryonic day 12.5 (E12.5) in the mouse. This view, however, is challenged by recent transcriptomics and genetic evidence. We therefore set out to investigate the fate and potency of TEC in the early thymus. Here using single cell (sc) RNAseq we identify a candidate mTEC progenitor population at E12.5, consistent with recent reports. Via lineage-tracing we demonstrate this population as mTEC fate-restricted, validating our bioinformatics prediction. Using potency analyses we also establish that most E11.5 and E12.5 progenitor TEC are cTEC-fated. Finally we show that overnight culture causes most if not all E12.5 cTEC-fated TEPC to acquire functional bipotency, and provide a likely molecular mechanism for this changed differentiation potential. Collectively, our data overturn the widely held view that a common TEPC predominates in the E12.5 thymus, showing instead that sublineage-primed progenitors are present from the earliest stages of thymus organogenesis but that these early fetal TEPC exhibit cell-fate plasticity in response to extrinsic factors. Our data provide a significant advance in the understanding of fetal thymic epithelial development and thus have implications for thymus-related clinical research, in particular research focussed on generating TEC from pluripotent stem cellshttps://www.frontiersin.org/articles/10.3389/fimmu.2023.1202163/fullthymusepithelial cellscell fatesingle celltranscriptomepotency |
| spellingShingle | Alison Mary Farley An Chengrui Sam Palmer Dong Liu Anastasia I. Kousa Paul Rouse Viktoria Major Joanna Sweetman Jan Morys Andrea Corsinotti Jennifer Nichols Janice Ure Renee McLay Luke Boulter S. Jon Chapman Simon R. Tomlinson C. Clare Blackburn Thymic epithelial cell fate and potency in early organogenesis assessed by single cell transcriptional and functional analysis Frontiers in Immunology thymus epithelial cells cell fate single cell transcriptome potency |
| title | Thymic epithelial cell fate and potency in early organogenesis assessed by single cell transcriptional and functional analysis |
| title_full | Thymic epithelial cell fate and potency in early organogenesis assessed by single cell transcriptional and functional analysis |
| title_fullStr | Thymic epithelial cell fate and potency in early organogenesis assessed by single cell transcriptional and functional analysis |
| title_full_unstemmed | Thymic epithelial cell fate and potency in early organogenesis assessed by single cell transcriptional and functional analysis |
| title_short | Thymic epithelial cell fate and potency in early organogenesis assessed by single cell transcriptional and functional analysis |
| title_sort | thymic epithelial cell fate and potency in early organogenesis assessed by single cell transcriptional and functional analysis |
| topic | thymus epithelial cells cell fate single cell transcriptome potency |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1202163/full |
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