Altered hematopoiesis in trisomy 21 as revealed through in vitro differentiation of isogenic human pluripotent cells
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.
| Errataetall: |
CommentIn: Nat Rev Cancer. 2012 Dec;12(12):799. - PMID 23151601 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2012 |
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| Erschienen: |
2012 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:109 |
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| Enthalten in: |
Proceedings of the National Academy of Sciences of the United States of America - 109(2012), 43 vom: 23. Okt., Seite 17567-72 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Maclean, Glenn A [VerfasserIn] |
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| Links: |
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| Themen: |
Journal Article |
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| Anmerkungen: |
Date Completed 07.01.2013 Date Revised 21.10.2021 published: Print-Electronic CommentIn: Nat Rev Cancer. 2012 Dec;12(12):799. - PMID 23151601 Citation Status MEDLINE |
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| doi: |
10.1073/pnas.1215468109 |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Altered hematopoiesis in trisomy 21 as revealed through in vitro differentiation of isogenic human pluripotent cells |
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| 500 | |a CommentIn: Nat Rev Cancer. 2012 Dec;12(12):799. - PMID 23151601 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
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| 700 | 1 | |a Menne, Tobias F |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Guoji |e verfasserin |4 aut | |
| 700 | 1 | |a Sanchez, Danielle J |e verfasserin |4 aut | |
| 700 | 1 | |a Park, In-Hyun |e verfasserin |4 aut | |
| 700 | 1 | |a Daley, George Q |e verfasserin |4 aut | |
| 700 | 1 | |a Orkin, Stuart H |e verfasserin |4 aut | |
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