Overlapping gene coexpression patterns in human medullary thymic epithelial cells generate self-antigen diversity
Promiscuous expression of numerous tissue-restricted self-antigens (TRAs) in medullary thymic epithelial cells (mTECs) is essential to safeguard self-tolerance. A distinct feature of promiscuous gene expression is its mosaic pattern (i.e., at a given time, each self-antigen is expressed only in 1-3%...
Gespeichert in:
| Hauptverfasser: | , , , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
August 26, 2013
|
| In: |
Proceedings of the National Academy of Sciences of the United States of America
Year: 2013, Jahrgang: 110, Heft: 37, Pages: E3497-E3505 |
| ISSN: | 1091-6490 |
| DOI: | 10.1073/pnas.1308311110 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1073/pnas.1308311110 Verlag, lizenzpflichtig, Volltext: https://www.pnas.org/content/110/37/E3497 |
| Verfasserangaben: | Sheena Pinto, Chloé Michel, Hannah Schmidt-Glenewinkel, Nathalie Harder, Karl Rohr, Stefan Wild, Benedikt Brors, and Bruno Kyewski |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1778928994 | ||
| 003 | DE-627 | ||
| 005 | 20230426131257.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 211124s2013 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1073/pnas.1308311110 |2 doi | |
| 035 | |a (DE-627)1778928994 | ||
| 035 | |a (DE-599)KXP1778928994 | ||
| 035 | |a (OCoLC)1341430866 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 32 |2 sdnb | ||
| 100 | 1 | |a Pinto, Sheena Dominique |e VerfasserIn |0 (DE-588)141388048 |0 (DE-627)627291090 |0 (DE-576)323638376 |4 aut | |
| 245 | 1 | 0 | |a Overlapping gene coexpression patterns in human medullary thymic epithelial cells generate self-antigen diversity |c Sheena Pinto, Chloé Michel, Hannah Schmidt-Glenewinkel, Nathalie Harder, Karl Rohr, Stefan Wild, Benedikt Brors, and Bruno Kyewski |
| 264 | 1 | |c August 26, 2013 | |
| 300 | |a 9 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 24.11.2021 | ||
| 520 | |a Promiscuous expression of numerous tissue-restricted self-antigens (TRAs) in medullary thymic epithelial cells (mTECs) is essential to safeguard self-tolerance. A distinct feature of promiscuous gene expression is its mosaic pattern (i.e., at a given time, each self-antigen is expressed only in 1-3% of mTECs). How this mosaic pattern is generated at the single-cell level is currently not understood. Here, we show that subsets of human mTECs expressing a particular TRA coexpress distinct sets of genes. We identified three coexpression groups comprising overlapping and complementary gene sets, which preferentially mapped to certain chromosomes and intrachromosomal gene clusters. Coexpressed gene loci tended to colocalize to the same nuclear subdomain. The TRA subsets aligned along progressive differentiation stages within the mature mTEC subset and, in vitro, interconverted along this sequence. Our data suggest that single mTECs shift through distinct gene pools, thus scanning a sizeable fraction of the overall repertoire of promiscuously expressed self-antigens. These findings have implications for the temporal and spatial (re)presentation of self-antigens in the medulla in the context of tolerance induction. | ||
| 650 | 4 | |a central tolerance | |
| 650 | 4 | |a human thymic epithelial cells | |
| 650 | 4 | |a promiscuous gene expression | |
| 700 | 1 | |a Michel, Chloé |e VerfasserIn |4 aut | |
| 700 | 1 | |a Schmidt-Glenewinkel, Hannah |e VerfasserIn |4 aut | |
| 700 | 1 | |a Harder, Nathalie |e VerfasserIn |0 (DE-588)1073949370 |0 (DE-627)830053417 |0 (DE-576)327502266 |4 aut | |
| 700 | 1 | |a Rohr, Karl |e VerfasserIn |0 (DE-588)137474466 |0 (DE-627)695829440 |0 (DE-576)303788593 |4 aut | |
| 700 | 1 | |a Wild, Stefan |e VerfasserIn |4 aut | |
| 700 | 1 | |a Brors, Benedikt |e VerfasserIn |0 (DE-588)1112102965 |0 (DE-627)866068732 |0 (DE-576)476376157 |4 aut | |
| 700 | 1 | |a Kyewski, Bruno |e VerfasserIn |0 (DE-588)1133586147 |0 (DE-627)889507392 |0 (DE-576)170754626 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |a National Academy of Sciences (Washington, DC) |t Proceedings of the National Academy of Sciences of the United States of America |d Washington, DC : National Acad. of Sciences, 1915 |g 110(2013), 37, Seite E3497-E3505 |h Online-Ressource |w (DE-627)254235379 |w (DE-600)1461794-8 |w (DE-576)073260509 |x 1091-6490 |7 nnas |
| 773 | 1 | 8 | |g volume:110 |g year:2013 |g number:37 |g pages:E3497-E3505 |g extent:9 |a Overlapping gene coexpression patterns in human medullary thymic epithelial cells generate self-antigen diversity |
| 856 | 4 | 0 | |u https://doi.org/10.1073/pnas.1308311110 |x Verlag |x Resolving-System |z lizenzpflichtig |3 Volltext |
| 856 | 4 | 0 | |u https://www.pnas.org/content/110/37/E3497 |x Verlag |z lizenzpflichtig |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20211124 | ||
| 993 | |a Article | ||
| 994 | |a 2013 | ||
| 998 | |g 1133586147 |a Kyewski, Bruno |m 1133586147:Kyewski, Bruno |d 50000 |e 50000PK1133586147 |k 0/50000/ |p 8 |y j | ||
| 998 | |g 1112102965 |a Brors, Benedikt |m 1112102965:Brors, Benedikt |d 700000 |d 716000 |e 700000PB1112102965 |e 716000PB1112102965 |k 0/700000/ |k 1/700000/716000/ |p 7 | ||
| 998 | |g 137474466 |a Rohr, Karl |m 137474466:Rohr, Karl |d 160000 |d 160100 |e 160000PR137474466 |e 160100PR137474466 |k 0/160000/ |k 1/160000/160100/ |p 5 | ||
| 998 | |g 1073949370 |a Harder, Nathalie |m 1073949370:Harder, Nathalie |d 700000 |d 706000 |e 700000PH1073949370 |e 706000PH1073949370 |k 0/700000/ |k 1/700000/706000/ |p 4 | ||
| 998 | |g 141388048 |a Pinto, Sheena Dominique |m 141388048:Pinto, Sheena Dominique |d 140000 |e 140000PP141388048 |k 0/140000/ |p 1 |x j | ||
| 999 | |a KXP-PPN1778928994 |e 400526302X | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"person":[{"family":"Pinto","given":"Sheena Dominique","display":"Pinto, Sheena Dominique","role":"aut"},{"family":"Michel","given":"Chloé","display":"Michel, Chloé","role":"aut"},{"role":"aut","given":"Hannah","display":"Schmidt-Glenewinkel, Hannah","family":"Schmidt-Glenewinkel"},{"role":"aut","family":"Harder","given":"Nathalie","display":"Harder, Nathalie"},{"display":"Rohr, Karl","given":"Karl","family":"Rohr","role":"aut"},{"role":"aut","display":"Wild, Stefan","given":"Stefan","family":"Wild"},{"display":"Brors, Benedikt","given":"Benedikt","family":"Brors","role":"aut"},{"role":"aut","display":"Kyewski, Bruno","given":"Bruno","family":"Kyewski"}],"recId":"1778928994","origin":[{"dateIssuedKey":"2013","dateIssuedDisp":"August 26, 2013"}],"name":{"displayForm":["Sheena Pinto, Chloé Michel, Hannah Schmidt-Glenewinkel, Nathalie Harder, Karl Rohr, Stefan Wild, Benedikt Brors, and Bruno Kyewski"]},"language":["eng"],"title":[{"title":"Overlapping gene coexpression patterns in human medullary thymic epithelial cells generate self-antigen diversity","title_sort":"Overlapping gene coexpression patterns in human medullary thymic epithelial cells generate self-antigen diversity"}],"physDesc":[{"extent":"9 S."}],"type":{"bibl":"article-journal","media":"Online-Ressource"},"id":{"eki":["1778928994"],"doi":["10.1073/pnas.1308311110"]},"relHost":[{"pubHistory":["1.1915 -"],"type":{"media":"Online-Ressource","bibl":"periodical"},"recId":"254235379","disp":"National Academy of Sciences (Washington, DC)Proceedings of the National Academy of Sciences of the United States of America","language":["eng"],"titleAlt":[{"title":"PNAS online"},{"title":"PNAS"}],"physDesc":[{"extent":"Online-Ressource"}],"id":{"issn":["1091-6490"],"zdb":["1461794-8"],"eki":["254235379"]},"part":{"pages":"E3497-E3505","year":"2013","volume":"110","text":"110(2013), 37, Seite E3497-E3505","issue":"37","extent":"9"},"note":["Gesehen am 09.03.2022"],"origin":[{"dateIssuedDisp":"1915-","publisher":"National Acad. of Sciences","publisherPlace":"Washington, DC","dateIssuedKey":"1915"}],"corporate":[{"display":"National Academy of Sciences","role":"aut"}],"title":[{"title":"Proceedings of the National Academy of Sciences of the United States of America","title_sort":"Proceedings of the National Academy of Sciences of the United States of America"}]}],"note":["Gesehen am 24.11.2021"]} | ||
| SRT | |a PINTOSHEENOVERLAPPIN2620 | ||