Regulation of Haematopoiesis in Homeostasis and Disease
Description of research
Blood stem cells need to both perpetuate (self-renew) themselves and differentiate into all mature blood cells to maintain blood formation throughout life. Clarifying how haemopoietic stem and progenitor cells (HSPCs) differentiate into diverse cell types is important for understanding how this process is subverted in the generation of blood pathologies.
The aim of our group is to decipher how differentiation pathways of HSPCs are influenced by different microenvironments. To achieve that we use state-of-the-art single-cell RNA-seq data generation combined with computational analysis to establish principles of blood lineage differentiation. In particularly we are focusing on the dissection of the heterogeneity of cellular states in the blood system. Our research involves the use of both model organism (zebrafish, Danio rerio) and human samples. Currently, we are working with human foetal haematopoietic cells to reveal the dynamics and cellular programmes active during human blood development as well as lung cancer patient samples to investigating the influence of tumour microenvironment in the context of pathological differentiation of myeloid progenitors.
The results from our studies will advance our understanding of how normal fate decisions are instigated and provide clues for the design of novel therapies for blood pathologies.
Tangherloni A, Ricciuti F, Besozzi D, Liò P, Cvejic A (2021). Analysis of single-cell RNA sequencing data based on autoencoders. BMC Bioinformatics. 2021 Jun 8;22(1):309.
Spencer Chapman M, Ranzoni AM, Myers B, Williams N, Coorens THH, Mitchell E, Butler T, Dawson KJ, Hooks Y, Moore L, Nangalia J, Robinson PS, Yoshida K, Hook E, Campbell PJ, Cvejic A (2021). Lineage tracing of human development through somatic mutations. Nature. 2021 Jul;595(7865):85-90.
Ranzoni AM, Tangherloni A, Berest I, Riva SG, Myers B, Strzelecka PM, Xu J, Panada E, Mohorianu I, Zaugg JB, Cvejic A (2020). Integrative Single-Cell RNA-Seq and ATAC-Seq Analysis of Human Developmental Hematopoiesis. Cell Stem Cell. 2020 Dec 15:S1934-5909(20)30553-1.
Canu G, Athanasiadis E, Grandy RA, Garcia-Bernardo J, Strzelecka PM, Vallier L, Ortmann D, Cvejic A (2020). Analysis of endothelial-to-haematopoietic transition at the single cell level identifies cell cycle regulation as a driver of differentiation. Genome Biol. 2020 Jul 1;21(1):157.
Bica I, Andrés-Terré H, Cvejic A*,♯, Liò P* (2020). Unsupervised Generative and Graph Representation Learning for Modelling Cell Differentiation. Sci Rep. 2020 Jun 17;10(1):9790. (♯corresponding author, *joint senior authors)
Hernández PP, Strzelecka PM, Athanasiadis EI, Hall D, Robalo AF, Collins CM, Boudinot P, Levraud JP, Cvejic A (2018). Single-cell transcriptional analysis reveals ILC-like cells in zebrafish. Sci Immunol, 2018 Nov 16;3(29). pii: eaau5265.
Athanasiadis EI, Botthof JG, Andres H, Ferreira L, Lio P, Cvejic A (2017). Single-cell RNA-sequencing uncovers transcriptional states and fate decisions in haematopoiesis. Nat Commun, 2017 Dec 11;8(1):2045.
Botthof JG, Bielczyk-Maczyńska E, Ferreira L, Cvejic A (2017). Loss of the homologous recombination gene rad51 leads to Fanconi anemia-like symptoms in zebrafish. Proc Natl Acad Sci U S A, 2017 May 30;114(22):E4452-E4461.
Carmona SJ, Teichmann SA*,♯, Ferreira L, Macaulay IC, Stubbington MJT, Cvejic A*,♯, Gfeller D*,♯ (2017). Single-cell transcriptome analysis of fish immune cells provides insight into the evolution of vertebrate immune cell types. Genome Research, 2017 Jan 13. pii: gr.207704.116. (♯corresponding author, *joint senior author)
Macaulay IC, Svensson V, Labalette C, Ferreira L, Hamey F, Voet T, Teichmann S, Cvejic A (2016). Single cell RNA-sequencing reveals a continuous spectrum of differentiation in haematopoietic cells. Cell Reports, 14(4):966-7.
Bielczyk-Maczyńska E, Lam Hung L, Ferreira L, Fleischmann T, Weis F, Fernández-Pevida A, Harvey SA, Wali N, Warren AJ, Barroso I, Stemple DL, Cvejic A (2015). The ribosome biogenesis protein Nol9 is essential for definitive hematopoiesis and pancreas morphogenesis in zebrafish. PLOS Genetics, 11(12):e1005677.