Document Detail


Trisomy 21-associated defects in human primitive hematopoiesis revealed through induced pluripotent stem cells.
MedLine Citation:
PMID:  23045704     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Patients with Down syndrome (trisomy 21, T21) have hematologic abnormalities throughout life. Newborns frequently exhibit abnormal blood counts and a clonal preleukemia. Human T21 fetal livers contain expanded erythro-megakaryocytic precursors with enhanced proliferative capacity. The impact of T21 on the earliest stages of embryonic hematopoiesis is unknown and nearly impossible to examine in human subjects. We modeled T21 yolk sac hematopoiesis using human induced pluripotent stem cells (iPSCs). Blood progenitor populations generated from T21 iPSCs were present at normal frequency and proliferated normally. However, their developmental potential was altered with enhanced erythropoiesis and reduced myelopoiesis, but normal megakaryocyte production. These abnormalities overlap with those of T21 fetal livers, but also reflect important differences. Our studies show that T21 confers distinct developmental stage- and species-specific hematopoietic defects. More generally, we illustrate how iPSCs can provide insight into early stages of normal and pathological human development.
Authors:
Stella T Chou; Marta Byrska-Bishop; Joanna M Tober; Yu Yao; Daniel Vandorn; Joanna B Opalinska; Jason A Mills; John Kim Choi; Nancy A Speck; Paul Gadue; Ross C Hardison; Richard L Nemiroff; Deborah L French; Mitchell J Weiss
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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:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  17573-8     Citation Subset:  IM    
Data Bank Information
Bank Name/Acc. No.:
GEO/GSE35561
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MeSH Terms
Descriptor/Qualifier:
Cell Differentiation
Down Syndrome*
Gene Expression Profiling
Hematopoiesis / genetics*
Humans
Pluripotent Stem Cells / cytology*
RNA, Messenger / genetics
Real-Time Polymerase Chain Reaction
Grant Support
ID/Acronym/Agency:
K08 HL093290/HL/NHLBI NIH HHS; P30 DK090969/DK/NIDDK NIH HHS; R01 DK065806/DK/NIDDK NIH HHS; R01 DK065806/DK/NIDDK NIH HHS; R01 HL091724/HL/NHLBI NIH HHS; R01 HL091724/HL/NHLBI NIH HHS; RC2 HG005573/HG/NHGRI NIH HHS; RC2 HL10166/HL/NHLBI NIH HHS; U01 HL099656/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/RNA, Messenger
Comments/Corrections
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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