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%...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Hauptverfasser: Pinto, Sheena Dominique (VerfasserIn) , Michel, Chloé (VerfasserIn) , Schmidt-Glenewinkel, Hannah (VerfasserIn) , Harder, Nathalie (VerfasserIn) , Rohr, Karl (VerfasserIn) , Wild, Stefan (VerfasserIn) , Brors, Benedikt (VerfasserIn) , Kyewski, Bruno (VerfasserIn)
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
Volltext
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