Perturbation of fetal liver hematopoietic stem and progenitor cell development by trisomy 21

Roy, Anindita, Cowan, Gillian, Mead, Adam J., Filippi, Sarah, Bohn, Georg, Chaidos, Aristeidis, Tunstall, Oliver, Chan, Jerry K. Y., Choolani, Mahesh, Bennett, Phillip, Kumar, Sailesh, Atkinson, Deborah, Wyatt-Ashmead, Josephine, Hu, Ming, Stumpf, Michael P. H., Goudevenou, Katerina, O'Connor, David, Chou, Stella T., Weiss, Mitchell J., Karadimitris, Anastasios, Jacobsen, Sten Eirik, Vyas, Paresh and Roberts, Irene (2012) Perturbation of fetal liver hematopoietic stem and progenitor cell development by trisomy 21. National Academy of Sciences. Proceedings, 109 43: 17579-17584. doi:10.1073/pnas.1211405109

Author Roy, Anindita
Cowan, Gillian
Mead, Adam J.
Filippi, Sarah
Bohn, Georg
Chaidos, Aristeidis
Tunstall, Oliver
Chan, Jerry K. Y.
Choolani, Mahesh
Bennett, Phillip
Kumar, Sailesh
Atkinson, Deborah
Wyatt-Ashmead, Josephine
Hu, Ming
Stumpf, Michael P. H.
Goudevenou, Katerina
O'Connor, David
Chou, Stella T.
Weiss, Mitchell J.
Karadimitris, Anastasios
Jacobsen, Sten Eirik
Vyas, Paresh
Roberts, Irene
Title Perturbation of fetal liver hematopoietic stem and progenitor cell development by trisomy 21
Journal name National Academy of Sciences. Proceedings   Check publisher's open access policy
ISSN 0027-8424
Publication date 2012-10-23
Year available 2012
Sub-type Article (original research)
DOI 10.1073/pnas.1211405109
Open Access Status Not yet assessed
Volume 109
Issue 43
Start page 17579
End page 17584
Total pages 6
Place of publication Washington, DC, United States
Publisher National Academy of Sciences
Language eng
Abstract 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.
Keyword Aneuploidy
Human fetus
Transient myeloproliferative disorder
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Chemistry and Molecular Biosciences
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