CRUK Career Development Fellow

Email: as889@cam.ac.uk

Research themes:

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.

Key Publications:

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.

Svensson V, Natarajan KN, Ly LH, Miragaia RJ, Labalette C, Macaulay IC, Cvejic A, Teichmann SA (2017) Power Analysis of Single Cell RNA‐Sequencing Experiments. Nature Methods, 14(4):381-387.

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)

Dee CT, Nagaraju TR, Athanasiadis EI, Gray C, del Ama LF, Johnston SA, Secombes CJ*^,♯, Cvejic A*^,♯, Hurlstone AFL*^,♯ (2016). CD4-Transgenic Zebrafish Reveals Tissue Resident T_H2- and T_reg-like T cell Populations and Diverse Mononuclear Phagocytes. The Journal of Immunology, 197(9):3520-30 (^♯corresponding author, *joint senior authors)

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.

Cvejic A (2016). Mechanisms of fate decision and lineage commitment during haematopoiesis. Immunology and Cell Biology, doi: 10.1038/icb.2015.96, Invited Review.

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.

Chen L, Kostadima M, [59 co-authors], Cvejic A, Soranzo N, Ouwehand WH, Stunnenberg HG, Frontini M, Rendon A (2014). Transcriptional diversity during lineage commitment of human blood progenitors. Science, 345(6204).

Bielczyk-Maczyńska E, Serbanovic-Canic J, Ferreira L, Soranzo N, Stemple D, Ouwehand WH, Cvejic A (2014). A loss of function screen of identified genome-wide association study loci reveals new genes controlling haematopoiesis. PLOS Genetics, 10(7):e1004450.

Cvejic A*^,♯, Haer-Wigman L*, Stephens JC*, Kostadima M, Smethurst PA, Frontini M, Sipos B, Akker Evd, Bertone P, Bielczyk E, Farrow S, Fehrmann RSN, Gray A, Haas M, Haver VG, Jordan G, Karjalainen J, Kerstens HHD, Kiddle G, Loyd-Jones H, Needs M, Poole J, Soussan A, Rendon A, Rieneck K, Sambrook JG, Schepers H, Siljer HHW, Swinkels D, Tamuri AU, Verweij N, Watkins NA, Westra HJ, Stemple D, Franke L, Soranzo N, Stunnenberg HG, Goldman N, Harst Pvd, C Schoot Evd, Ouwehand WH^♯, Albers C^♯ (2013). The red blood cell GWAS gene SMIM1 underlies the Vel blood group and is a novel regulator of red blood cell formation. Nature Genetics, 45(5):542-5. (^♯corresponding author, *joint first authors)