Document Detail

Altered hematopoiesis in trisomy 21 as revealed through in vitro differentiation of isogenic human pluripotent cells.
MedLine Citation:
PMID:  23045682     Owner:  NLM     Status:  MEDLINE    
Trisomy 21 is associated with hematopoietic abnormalities in the fetal liver, a preleukemic condition termed transient myeloproliferative disorder, and increased incidence of acute megakaryoblastic leukemia. Human trisomy 21 pluripotent cells of various origins, human embryonic stem (hES), and induced pluripotent stem (iPS) cells, were differentiated in vitro as a model to recapitulate the effects of trisomy on hematopoiesis. To mitigate clonal variation, we isolated disomic and trisomic subclones from the same parental iPS line, thereby generating subclones isogenic except for chromosome 21. Under differentiation conditions favoring development of fetal liver-like, γ-globin expressing, definitive hematopoiesis, we found that trisomic cells of hES, iPS, or isogenic origins exhibited a two- to fivefold increase in a population of CD43(+)(Leukosialin)/CD235(+)(Glycophorin A) hematopoietic cells, accompanied by increased multilineage colony-forming potential in colony-forming assays. These findings establish an intrinsic disturbance of multilineage myeloid hematopoiesis in trisomy 21 at the fetal liver stage.
Glenn A Maclean; Tobias F Menne; Guoji Guo; Danielle J Sanchez; In-Hyun Park; George Q Daley; Stuart H Orkin
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; 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:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  17567-72     Citation Subset:  IM    
Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA.
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MeSH Terms
Cell Differentiation*
Down Syndrome*
Gene Expression Profiling
Pluripotent Stem Cells / cytology*
Polymerase Chain Reaction
Grant Support
U01 HL 10001/HL/NHLBI NIH HHS; U01 HL100001/HL/NHLBI NIH HHS; //Howard Hughes Medical Institute
Comment In:
Nat Rev Cancer. 2012 Dec;12(12):799   [PMID:  23151601 ]

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