Group Carolina Guibentif

Research summary

Our overall goal is to establish a new framework for the identification of prenatal transformation events leading to childhood leukemia.

Half of all childhood cancers have a suspected prenatal origin, which limits access to the cancer-initiating developmental progenitor. Human pluripotent stem cells (hPSCs) can be differentiated in vitro, mimicking defined processes of embryonic development, and thus represent a promising tool to dissect the molecular mechanisms of malignant transformation taking place in prenatal cell populations.

Hematological malignancies constitute a particular challenge, as the hematopoietic system develops through successive waves, in multiple anatomical locations and embryonic developmental time-points. The molecular mechanisms regulating the emergence and specialization of these successive embryonic blood progenitors are currently under investigation. Moreover, the correlation between developmental processes leading to blood formation during hPSC differentiation vs corresponding blood waves in the embryo remain to be systematically established.

Our research employs a cross-species approach, and harnesses emerging single-cell profiling technology, to bridge hPSC-based in vitro models of human embryonic development with the latest progress in developmental hematopoiesis studied in vivo in the mouse.

Our goal is to chart the diversity of hematopoietic waves occurring in vitro, in order to identify and characterize the developmental populations susceptible to transformation that lead to childhood leukemia.

Research tools and resources

Our cross-species approach involves both mouse models of in vivo embryonic hematopoiesis and in vitro human pluripotent stem cell culture and differentiation. Analysis tools include single-cell profiling technology, multicolor flow cytometry analysis and sorting, and hematopoietic in vitro functional assays.

Current group members

Carolina Guibentif, PhD, Principal investigator (Junior PI)
Anna Hogmalm, PhD
Pavan Kumar, PhD, Postdoc
Robel Tesfaye, PhD, Postdoc
Anuntxi Monsalve, PhD student

Selected publications

1. An atlas of rabbit development as a model for single-cell comparative genomics.
   Ton MN, Keitley D, Theeuwes B, Guibentif C, Ahnfelt-Rønne J, Andreassen TK, Calero-Nieto FJ, Imaz-Rosshandler I, Pijuan-Sala B, Nichols J, Benito-Gutiérrez È, Marioni JC, Göttgens B.Nat Cell Biol. 2023 Jul;25(7):1061-1072. doi: 10.1038/s41556-023-01174-0.
    

2. Stabilized mosaic single-cell data integration using unshared features.
   Ghazanfar S, Guibentif C, Marioni JC.Nat Biotechnol. 2023 May 25. doi: 10.1038/s41587-023-01766-z. 
    

3. Mesp1 controls the chromatin and enhancer landscapes essential for spatiotemporal patterning of early cardiovascular progenitors.
   Lin X, Swedlund B, Ton M-L N, Ghazanfar S, Guibentif C, Paulissen C, Baudelet E, Plaindoux E, Achouri Y, Calonne E, Dubois C, Mansfield W, Zaffran S, Marioni JC, Fuks F, Göttgens B, Lescroart F, Blanpain C. Nature Cell Biology. 2022 Vol. 24, issue 7, p1114-1128
    

4. Pyruvate metabolism guides definitive lineage specification during hematopoietic emergence.
   Oburoglu L, Mansell E, Canals I, Sigurdsson V, Guibentif C, Soneji S, Woods N-B. EMBO Reports. 2022 Vol.23, issue 2, e54384
    

5. Coordinated Changes in Gene Expression Kinetics Underlie both Mouse and Human Erythroid Maturation.
   Barile M, Imaz-Rosshandler I., Inzani I., Ghazanfar S., John C. Marioni, Guibentif C.*, Göttgens B*. Genome Biology. 2021 Vol. 22, issue 1, p197 (* co-corresponding authors)
    
6. Integration of spatial and single cell transcriptomic data elucidates mouse organogenesis. 
   Lohoff T., Ghazanfar S., Missarova A., Koulena N., Pierson N., Griffiths J.A., Bardot E., Eng C-H.L., Tyser R.C.V., Argelaguet R., Guibentif C., Srivinas S., Briscoe J., Simons B.D., Hadjantonakis A.K., Goettgens B., Reik W., Nichols J., Cai L., Marioni J.C. Nature Biotechnology. 2021
    
7. Diverse Routes towards Early Somites in the Mouse Embryo.
   Guibentif C.*, Griffiths J.A.*, Imaz-Rosshandler I., Ghazanfar S., Wilson V., Nichols J., Göttgens B., Marioni J.C. Developmental Cell. 2021 Vol. 56, issue 1, p141-153 (* equal contribution)
    
8. Single cell genomics and developmental biology: moving beyond the generation of cell type catalogues. (Review)
   Ton M-L N., Guibentif C., Göttgens B. Current Opinion in Genetics and Development. 2020 Vol. 64, p66-71
    
9. A single-cell molecular map of mouse gastrulation and early organogenesis.
   Pijuan-Sala B.*, Griffiths J.A.*, Guibentif C.*, Hiscock TW, Jawaid W, Calero-Nieto FJ, Mulas C, Ibarra-Soria X, Tyser RCV, Ho DLL, Reik W, Srinivas S, Simons BD, Nichols J, Marioni JC, Göttgens B. Nature. 2019 Vol. 566, issue 7745, p490-495 (* equal contribution)
    
10. Single-cell transcriptional profiling: a window into embryonic cell-type specification. (Review)
    Pijuan-Sala B., Guibentif C., Göttgens B. Nature Reviews Molecular Cell Biology. 2018 19(6):399-412
     
11. Blood: Education for stem cells. (News and Views)
    Guibentif C., Göttgens B. Nature. 2017; Vol. 545, issue 7655, p415-417
     
12. Single-Cell Analysis Identifies Distinct Stages of Human Endothelial-to-Hematopoietic Transition.
    Guibentif C., Rönn R.E., Böiers C., Lang S., Saxena S., Soneji S., Enver T., Karlsson G., Woods N.-B.  Cell Reports. 2017 Vol. 19, issue 1, p10–19

More group Carolina Guibentif publications on PubMed