Studies in an Early Development Window Unveils a Severe HSC Defect in both Murine and Human Fanconi Anemia.
Stem Cell Reports
; 11(5): 1075-1091, 2018 11 13.
Article
em En
| MEDLINE
| ID: mdl-30449320
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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Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Hematopoéticas
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Desenvolvimento Embrionário
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Anemia de Fanconi
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article