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
Athul Venu Beena, PhD student
Elin Hilpold Berntsson, PhD student

Selected publications

1. Resolving thyroid lineage cell trajectories merging into a dual endocrine gland in mammals. 
   Lobo M, Johansson E, Kumari S, Schoultz E, Ahlinder I, Liang S, Carlsson T, Johansson BR, Marotta P, De Felice M, Dahlberg J, Guibentif C, Fagman H, Maehr R, Nilsson M. Nature Communications. 2026 May 25;17(1):6811. 
    
2. A single-cell and tissue-scale analysis suite resolves Mixl1's role in heart development. 
   Strauss ME, Ton MN, Mason S, Bagri J, Harland LTG, Imaz-Rosshandler I, Wilson NK, Nichols J, Tyser RCV, Göttgens B, Marioni JC, Guibentif C. iScience. 2025 Apr 10;28(5):112397. 
    
3. Defective ribosome assembly impairs leukemia progression in a murine model of acute myeloid leukemia. 
   Sjövall D, Ghosh S, Fernandez-Fuentes N, Velasco-Hernandez T, Hogmalm A, Menendez P, Hansson J, Guibentif C, Jaako P. Cell Reports. 2024 Nov 26;43(11):114864.
    
4. Tracking early mammalian organogenesis - prediction and validation of differentiation trajectories at whole organism scale.
   Imaz-Rosshandler I*, Rode C*, Guibentif C*, Harland LTG*, Ton MN, Dhapola P, Keitley D, Argelaguet R, Calero-Nieto FJ, Nichols J, Marioni JC, de Bruijn MFTR, Göttgens B. Development. 2024 Feb 1;151(3):dev201867. (* equal contribution)
    
5. 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.
    
6. Stabilized mosaic single-cell data integration using unshared features.
   Ghazanfar S, Guibentif C, Marioni JC.Nat Biotechnol. 2023 May 25. 
    
7. 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)
    
8. 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
    
9. 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)
    
10. 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)
     
11. 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