Leveraging single-cell ATAC-seq data to gain insights into the cell-type selective component of the human pancreatic islet regulome
ATAC-seq is essential for profiling chromatin accessibility and characterizing the transcriptional regulatory landscape. However, the recent shift towards the study of heterogeneous cell populations poses a challenge for bulk ATAC-seq. Thus, single-cell ATAC-seq has emerged as a response to the limi...
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| Formato: | tesis de maestría |
| Fecha de publicación: | 2021 |
| País: | España |
| Recursos: | Universitat Oberta de Catalunya (UOC) |
| Repositorio: | O2, repositorio institucional de la UOC |
| OAI Identifier: | oai:openaccess.uoc.edu:10609/134326 |
| Acesso em linha: | http://hdl.handle.net/10609/134326 |
| Access Level: | acceso abierto |
| Palavra-chave: | human pancreatic islet genome regulation genetic illot pancreàtic humà regulació genòmica genètica islote pancreático humano regulación genómica genética Pancreas -- TFM Pàncrees -- TFM Páncreas -- TFM |
| Resumo: | ATAC-seq is essential for profiling chromatin accessibility and characterizing the transcriptional regulatory landscape. However, the recent shift towards the study of heterogeneous cell populations poses a challenge for bulk ATAC-seq. Thus, single-cell ATAC-seq has emerged as a response to the limitations of bulk ATACseq when studying cellular heterogeneity. We aim to to characterize the cell-typeselective component of enhancers using scATAC-seq data. To achieve this purpose, we a) annotate regulome signatures across cell-type selective open chromatin regions, b) estimate TF motif enrichment among cell-type selective enhancers, c) detect accessible cell-type selective enhancers that show robust TF binding and d) identify T2D-associated SNPs affecting TF binding across celltype selective enhancers. Motif enrichment analysis presented well-defined groups of TF motifs enriched across islet cell-type selective enhancers. TF motif occurrences across cell-type selective enhancers showed that enhancers bound by a given TF was consistent with the cell-type selective clustering observed in the TF motif enrichment analysis. Finally, the integration of TF-binding characterizing islet cell-type enhancers with fine-mapped T2D genetic variants allowed us to propose the most likely molecular mechanism underlying a few T2D risk loci. |
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