| Perturbation of fetal liver hematopoietic stem and progenitor cell development by trisomy 21. | |
| | |
MedLine Citation:
|
PMID: 23045701 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
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: 2013-02-19 |
Medline Journal Info:
|
Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
|
Languages: eng Pagination: 17579-84 Citation Subset: IM |
Affiliation:
|
Centre for Haematology, Imperial College London, London W12 0NN, United Kingdom. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Cell Differentiation Cell Lineage Down Syndrome* Flow Cytometry Gene Expression Profiling Hematopoietic Stem Cells / pathology* Humans Liver / embryology*, pathology |
| Grant Support | |
ID/Acronym/Agency:
|
//Medical Research Council |
| 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
Previous Document: PKA and GAB2 play central roles in the FSH signaling pathway to PI3K and AKT in ovarian granulosa ce...
Next Document: Precise probes of type II interferon activity define the origin of interferon signatures in target t...