Fanconi anemia (FA) is a genetically heterogeneous, autosomal recessive disorder 
characterized by pediatric bone marrow failure and congenital anomalies. The 
effect of FA gene deficiency on hematopoietic development in utero remains 
poorly described as mouse models of FA do not develop hematopoietic failure and 
such studies cannot be performed on patients. We have created a human-specific 
in vitro system to study early hematopoietic development in FA using a 
lentiviral RNA interference (RNAi) strategy in human embryonic stem cells 
(hESCs). We show that knockdown of FANCA and FANCD2 in hESCs leads to a 
reduction in hematopoietic fates and progenitor numbers that can be rescued by 
FA gene complementation. Our data indicate that hematopoiesis is impaired in FA 
from the earliest stages of development, suggesting that deficiencies in 
embryonic hematopoiesis may underlie the progression to bone marrow failure in 
FA. This work illustrates how hESCs can provide unique insights into human 
development and further our understanding of genetic disease.