Title: "Computational analysis of Innate Lymphoid Cell ontogeny during embryogenesis"

Friday, November 8, 2024 at 2pm

Auditorium - CIML - 163 Av. de Luminy, 13009 Marseille

Composition du jury: 

- Christine Brun (President)

- Morgane Thomas-Chollier (Reviewer)

- Christelle Harly (Reviewer)

- Rachel Golub (Examiner)

- Stéphane Mancini (Guest)

- Serge van de Pavert (Supervisor)

- Denis Puthier (Co-supervisor)
 

Abstract: 

In recent years, single-cell RNA-sequencing and spatial transcriptomics methods have revolutionized the field of transcriptomics by enabling the analysis of gene expression with unprecedented resolution, down to the subcellular level. These cutting-edge techniques have opened new horizons for uncovering complex cellular heterogeneity within tissues and understanding the underlying biological processes, such as cell differentiation. My project took advantage of these powerful techniques to unravel the differentiation processes involved in the innate lymphoid cells (ILC) differentiation during embryogenesis at a single-cell level.

While single-cell RNA-sequencing has gained widespread popularity across various fields, including immunology, oncology, and developmental biology, the analysis of this data remains challenging, underscoring the need to develop new tools. A notable challenge is being able to distinguish cell populations in a continuum as these cells have highly similar transcriptomic profiles. Indeed, conventional methods examine cells in a gene-centric approach which overlooks the collective behavior of gene regulation. During my PhD, I faced this problem and was unable to clearly distinguish cell populations involved in ILC ontogeny using conventional methods.

To overcome this limitation, I developed SciGeneX, a novel tool that, unlike conventional methods, focuses on co-regulation of genes. This approach shifts the focus from analyzing cells to examining gene expression patterns across cell populations, and thus to help identify cell populations using combination of activation and repression of gene modules. With SciGeneX, I was able to identify the specific ILC populations involved in differentiation including mature ILC populations with their distribution increasing as embryogenesis progresses. I revealed key gene modules that are either activated or repressed during the ILC differentiation process and thereby reveal the differentiation pathways present within the embryo.

Recognizing the need for advanced tools beyond single-cell analysis, I also contributed to the development of a separate tool, STarlight, designed for the analysis of spatial transcriptomic data. STarlight allows for the analysis of spatial transcriptomics data independently of cell segmentation, providing a flexible and robust approach for studying gene expression in spatial context.