TY - JOUR
T1 - Fetal origins of hematopoietic failure in a murine model of Fanconi anemia
AU - Kamimae-Lanning, Ashley N.
AU - Goloviznina, Natalya A.
AU - Kurre, Peter
N1 - Funding Information:
The authors thank Dr. Amy Skinner, Dr. Jianya Huan, Tae Hoon Ha, Kyle Lenz, Andrea McBeth, Pamela Canaday, Dorian La Tocha, and the Oregon Health and Science University Cytogenetics Core. A.N.K.-L. was supported by T32 Molecular Hematology Training Grant HL778116 and N.L. Tartar Trust Grant. Presented in part at the 23rd Annual Fanconi Anemia Research Fund Scientific Symposium, Barcelona, Spain, 2011, and the 53rd Annual Meeting of the American Society of Hematology, San Diego, CA, 2011.
Funding Information:
A.N.K.-L. was supported by T32 Molecular Hematology Training Grant HL778116 and N.L. Tartar Trust Grant. Presented in part at the 23rd Annual Fanconi Anemia Research Fund Scientific Symposium, Barcelona, Spain, 2011, and the 53rd Annual Meeting of the American Society of Hematology, San Diego, CA, 2011.
Publisher Copyright:
© 2013 by The American Society of Hematology.
PY - 2013
Y1 - 2013
N2 - Hematopoietic failure is the predominant clinical manifestation of Fanconi anemia (FA), a rare, recessively inherited disorder. Mutations in 1 of 15 genes that coordinately function in a complex pathway to maintain DNA integrity also predispose patients to constitutional defects in growth and development. The hematologic manifestations have been considered to reflect the progressive loss of stem cells from the postnatal bone marrow microenvironment. Ethical concerns preclude the study of human hematopoiesis in utero. We report significant late gestational lethality and profound quantitative and qualitative deficiencies in the murine Fancc-/- fetal liver hematopoietic stem and progenitor cell pool. Fancc-/- fetal liver hematopoietic stem and progenitor cells revealed a significant loss of quiescence and decline in serial repopulating capacity, but no substantial difference in apoptosis or levels of reactive oxygen species. Our studies suggest that compromised hematopoiesis in Fancc-/- animals is developmentally programmed and does not arise de novo in bone marrow.
AB - Hematopoietic failure is the predominant clinical manifestation of Fanconi anemia (FA), a rare, recessively inherited disorder. Mutations in 1 of 15 genes that coordinately function in a complex pathway to maintain DNA integrity also predispose patients to constitutional defects in growth and development. The hematologic manifestations have been considered to reflect the progressive loss of stem cells from the postnatal bone marrow microenvironment. Ethical concerns preclude the study of human hematopoiesis in utero. We report significant late gestational lethality and profound quantitative and qualitative deficiencies in the murine Fancc-/- fetal liver hematopoietic stem and progenitor cell pool. Fancc-/- fetal liver hematopoietic stem and progenitor cells revealed a significant loss of quiescence and decline in serial repopulating capacity, but no substantial difference in apoptosis or levels of reactive oxygen species. Our studies suggest that compromised hematopoiesis in Fancc-/- animals is developmentally programmed and does not arise de novo in bone marrow.
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U2 - 10.1182/blood-2012-06-439679
DO - 10.1182/blood-2012-06-439679
M3 - Article
C2 - 23315168
AN - SCOPUS:84877629411
SN - 0006-4971
VL - 121
SP - 2008
EP - 2012
JO - Blood
JF - Blood
IS - 11
ER -