Perturbation of fetal liver hematopoietic stem and progenitor cell development by trisomy 21
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-eryth...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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National Academy of Sciences
2012
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| _version_ | 1824459322267009024 |
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| author | Roy, A Cowan, G Mead, AJ Filippi, S Bohn, G Chaidos, A Tunstall, O Chan, JKY Choolani, M Bennett, P Kumar, S Atkinson, D Wyatt-Ashmead, J Hu, M Stumpf, MPH Goudevenou, K O'Connor, D Chou, ST Weiss, MJ Karadimitris, A Jacobsen, SE Vyas, P Roberts, I |
| author_facet | Roy, A Cowan, G Mead, AJ Filippi, S Bohn, G Chaidos, A Tunstall, O Chan, JKY Choolani, M Bennett, P Kumar, S Atkinson, D Wyatt-Ashmead, J Hu, M Stumpf, MPH Goudevenou, K O'Connor, D Chou, ST Weiss, MJ Karadimitris, A Jacobsen, SE Vyas, P Roberts, I |
| author_sort | Roy, A |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T02:37:54Z |
| format | Journal article |
| id | oxford-uuid:a966c292-f956-4b0b-9172-20e7394936c9 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2025-02-19T04:39:56Z |
| publishDate | 2012 |
| publisher | National Academy of Sciences |
| record_format | dspace |
| spelling | oxford-uuid:a966c292-f956-4b0b-9172-20e7394936c92025-02-14T11:49:35ZPerturbation of fetal liver hematopoietic stem and progenitor cell development by trisomy 21Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a966c292-f956-4b0b-9172-20e7394936c9EnglishSymplectic Elements at OxfordNational Academy of Sciences2012Roy, ACowan, GMead, AJFilippi, SBohn, GChaidos, ATunstall, OChan, JKYChoolani, MBennett, PKumar, SAtkinson, DWyatt-Ashmead, JHu, MStumpf, MPHGoudevenou, KO'Connor, DChou, STWeiss, MJKaradimitris, AJacobsen, SEVyas, PRoberts, IThe 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. |
| spellingShingle | Roy, A Cowan, G Mead, AJ Filippi, S Bohn, G Chaidos, A Tunstall, O Chan, JKY Choolani, M Bennett, P Kumar, S Atkinson, D Wyatt-Ashmead, J Hu, M Stumpf, MPH Goudevenou, K O'Connor, D Chou, ST Weiss, MJ Karadimitris, A Jacobsen, SE Vyas, P Roberts, I Perturbation of fetal liver hematopoietic stem and progenitor cell development by trisomy 21 |
| title | Perturbation of fetal liver hematopoietic stem and progenitor cell development by trisomy 21 |
| title_full | Perturbation of fetal liver hematopoietic stem and progenitor cell development by trisomy 21 |
| title_fullStr | Perturbation of fetal liver hematopoietic stem and progenitor cell development by trisomy 21 |
| title_full_unstemmed | Perturbation of fetal liver hematopoietic stem and progenitor cell development by trisomy 21 |
| title_short | Perturbation of fetal liver hematopoietic stem and progenitor cell development by trisomy 21 |
| title_sort | perturbation of fetal liver hematopoietic stem and progenitor cell development by trisomy 21 |
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