Document Detail

Perturbation of fetal liver hematopoietic stem and progenitor cell development by trisomy 21.
MedLine Citation:
PMID:  23045701     Owner:  NLM     Status:  MEDLINE    
The 40-fold increase in childhood megakaryocyte-erythroid and B-cell leukemia in Down syndrome implicates trisomy 21 (T21) in perturbing fetal hematopoiesis. Here, we show that compared with primary disomic controls, primary T21 fetal liver (FL) hematopoietic stem cells (HSC) and megakaryocyte-erythroid progenitors are markedly increased, whereas granulocyte-macrophage progenitors are reduced. Commensurately, HSC and megakaryocyte-erythroid progenitors show higher clonogenicity, with increased megakaryocyte, megakaryocyte-erythroid, and replatable blast colonies. Biased megakaryocyte-erythroid-primed gene expression was detected as early as the HSC compartment. In lymphopoiesis, T21 FL lymphoid-primed multipotential progenitors and early lymphoid progenitor numbers are maintained, but there was a 10-fold reduction in committed PreproB-lymphoid progenitors and the functional B-cell potential of HSC and early lymphoid progenitor is severely impaired, in tandem with reduced early lymphoid gene expression. The same pattern was seen in all T21 FL samples and no samples had GATA1 mutations. Therefore, T21 itself causes multiple distinct defects in FL myelo- and lymphopoiesis.
Anindita Roy; Gillian Cowan; Adam J Mead; Sarah Filippi; Georg Bohn; Aristeidis Chaidos; Oliver Tunstall; Jerry K Y Chan; Mahesh Choolani; Phillip Bennett; Sailesh Kumar; Deborah Atkinson; Josephine Wyatt-Ashmead; Ming Hu; Michael P H Stumpf; Katerina Goudevenou; David O'Connor; Stella T Chou; Mitchell J Weiss; Anastasios Karadimitris; Sten Eirik Jacobsen; Paresh Vyas; Irene Roberts
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-10-08
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  109     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-24     Completed Date:  2013-01-07     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  17579-84     Citation Subset:  IM    
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MeSH Terms
Cell Differentiation
Cell Lineage
Down Syndrome*
Flow Cytometry
Gene Expression Profiling
Hematopoietic Stem Cells / pathology*
Liver / embryology*,  pathology
Grant Support
G0501838//Medical Research Council; G0801073//Medical Research Council; G1002092//Medical Research Council; //Medical Research Council
Comment In:
Nat Rev Cancer. 2012 Dec;12(12):799   [PMID:  23151601 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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