2024-03-29T05:58:07Zhttps://www.tdx.cat/oai/requestoai:www.tdx.cat:10803/6879442024-03-15T10:57:35Zcom_10803_236col_10803_690278
nam a 5i 4500
Single-cell RNA-sequencing
Sampling artifacts
Tonsil
Human Cell Atlas
Richter’s transformation
Seqüenciació d’ARN de cèl·lules individuals
Artefactes de mostreig
Amígdala
Atles de Cèl·lules Humanes
Transformació de Richter
Charting the heterogeneity of healthy and malignant immune cells, one cell at a time
[Barcelona] :
Universitat Pompeu Fabra,
2023
Accés lliure
http://hdl.handle.net/10803/687944
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Massoni Badosa, Ramon,
autor
Programa de doctorat en Biomedicina,
degree
1 recurs en línia (264 pàgines)
Tesi
Doctorat
Universitat Pompeu Fabra. Departament de Medicina i Ciències de la Vida
2023
Universitat Pompeu Fabra. Departament de Medicina i Ciències de la Vida
Tesis i dissertacions electròniques
Heyn, Holger,
supervisor acadèmic
Martín-Subero, José Ignacio,
supervisor acadèmic
TDX
Specialization and plasticity are hallmarks of immune cells. Thus, charting their heterogeneity is crucial to understand their function and role in diseases. In this setting, single-cell RNA-sequencing (scRNA-seq) has emerged as the leading technology to map cell-cell variability at unprecedented resolution. However, scRNA-seq suffers from numerous technical artifacts, which can lead to false conclusions if not accounted for. This thesis uses scRNA-seq in three studies. First, we study the effect of time at room temperature before cryopreservation on single-cell transcriptomes, and propose experimental and computational solutions to mitigate it. Second, we created an atlas of cell types and states in human tonsils, which are a model secondary lymphoid organ (SLO). We discover previously uncharacterized heterogeneity in slan+ cells and T-cells. In the third and final chapter, we chart the clonal evolution of chronic lymphocytic leukemia (CLL) to Richter’s transformation (RT). We show that RT cells are present already at diagnosis and are detectable with scRNA-seq. In addition, we quantify the transcriptomic changes associated with RT, revealing a characteristic OXPHOShighBCRlow axis of variability. Finally, all the code, data and papers derived from this thesis follow the FAIR principles: findable, accessible, interoperable, and reusable; which are vital features of responsible scientific research.
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