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A cell atlas of human thymic development defines T cell repertoire formation

ABSTRACT: We performed single-cell RNA-sequencing to create a cell census of the human thymus during development, early childhood and adult life. We sampled 15 embryonic and fetal thymi spanning thymic developmental stages between 7 post-conception weeks (PCW) to 17 PCW, and 9 postnatal thymi from paediatric and adult samples. We compared the cellular composition and T cell differentiation within human and mouse thymus using newly generated and repository mouse datasets. Finally, we investigated the bias in the recombination and selection of human versus mouse TCR repertoires.

INSTRUMENT(S): Illumina HiSeq 4000

ORGANISM(S): Mus musculus

SUBMITTER: Jong-Eun Park 

PROVIDER: E-MTAB-8581 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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A cell atlas of human thymic development defines T cell repertoire formation.

Park Jong-Eun JE   Botting Rachel A RA   Domínguez Conde Cecilia C   Popescu Dorin-Mirel DM   Lavaert Marieke M   Kunz Daniel J DJ   Goh Issac I   Stephenson Emily E   Ragazzini Roberta R   Tuck Elizabeth E   Wilbrey-Clark Anna A   Roberts Kenny K   Kedlian Veronika R VR   Ferdinand John R JR   He Xiaoling X   Webb Simone S   Maunder Daniel D   Vandamme Niels N   Mahbubani Krishnaa T KT   Polanski Krzysztof K   Mamanova Lira L   Bolt Liam L   Crossland David D   de Rita Fabrizio F   Fuller Andrew A   Filby Andrew A   Reynolds Gary G   Dixon David D   Saeb-Parsy Kourosh K   Lisgo Steven S   Henderson Deborah D   Vento-Tormo Roser R   Bayraktar Omer A OA   Barker Roger A RA   Meyer Kerstin B KB   Saeys Yvan Y   Bonfanti Paola P   Behjati Sam S   Clatworthy Menna R MR   Taghon Tom T   Haniffa Muzlifah M   Teichmann Sarah A SA  

Science (New York, N.Y.) 20200201 6480

The thymus provides a nurturing environment for the differentiation and selection of T cells, a process orchestrated by their interaction with multiple thymic cell types. We used single-cell RNA sequencing to create a cell census of the human thymus across the life span and to reconstruct T cell differentiation trajectories and T cell receptor (TCR) recombination kinetics. Using this approach, we identified and located in situ CD8αα<sup>+</sup> T cell populations, thymic fibroblast subtypes, and  ...[more]

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