Studies in an Early Development Window Unveils a Severe HSC Defect in both Murine and Human Fanconi Anemia - Imagerie Cellulaire et Cytométrie de Flux Access content directly
Journal Articles Stem Cell Reports Year : 2018

Studies in an Early Development Window Unveils a Severe HSC Defect in both Murine and Human Fanconi Anemia

Carine Domenech
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Loïc Maillard
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Fabien Guimiot
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Sandra Sanfilippo
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Sebastien Jacques
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Pierre de La Grange
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Noemie Robil
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Abstract

Fanconi anemia (FA) causes bone marrow failure early during childhood, and recent studies indicate that a hematopoietic defect could begin in utero. We performed a unique kinetics study of hematopoiesis in Fancg−/− mouse embryos, between the early embryonic day 11.5 (E11.5) to E12.5 developmental window (when the highest level of hematopoietic stem cells [HSC] amplification takes place) and E14.5. This study reveals a deep HSC defect with exhaustion of proliferative and self-renewal capacities very early during development, together with severe FA clinical and biological manifestations, which are mitigated at E14.5 due to compensatory mechanisms that help to ensure survival of Fancg−/− embryos. It also reports that a deep HSC defect is also observed during human FA development, and that human FA fetal liver (FL) HSCs present a transcriptome profile similar to that of mouse E12.5 Fancg−/− FL HSCs. Altogether, our results highlight that early mouse FL could represent a good alternative model for studying Fanconi pathology.
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hal-01945976 , version 1 (05-12-2018)

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Carine Domenech, Loïc Maillard, Alix Rousseau, Fabien Guidez, Laurence Petit, et al.. Studies in an Early Development Window Unveils a Severe HSC Defect in both Murine and Human Fanconi Anemia. Stem Cell Reports, 2018, 11 (5), pp.1075-1091. ⟨10.1016/j.stemcr.2018.10.001⟩. ⟨hal-01945976⟩
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