Prdm16 is a physiologic regulator of hematopoietic stem cells

Fetal liver and adult bone marrow hematopoietic stem cells (HSCs) renew or differentiate into committed progenitors to generate all blood cells. PRDM16 is involved in human leukemic translocations and is expressed highly in some karyotypically normal acute myeloblastic leukemias. As many genes invol...

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Bibliographic Details
Published in:Blood 2011-05, Vol.117 (19), p.5057-5066
Main Authors: Aguilo, Francesca, Avagyan, Serine, Labar, Amy, Sevilla, Ana, Lee, Dung-Fang, Kumar, Parameet, Lemischka, Ihor R., Zhou, Betty Y., Snoeck, Hans-Willem
Format: Article
Language:English
Subjects:
Animals
Apoptosis - physiology
Cell Differentiation - physiology
Cell Separation
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Flow Cytometry
Gene Expression
Gene Expression Profiling
Genotype
Hematopoiesis - physiology
Hematopoiesis and Stem Cells
Hematopoietic Stem Cells - cytology
Hematopoietic Stem Cells - physiology
Mice
Mice, Inbred C57BL
Mice, Knockout
Reverse Transcriptase Polymerase Chain Reaction
Transcription Factors - genetics
Transcription Factors - metabolism
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Summary:Fetal liver and adult bone marrow hematopoietic stem cells (HSCs) renew or differentiate into committed progenitors to generate all blood cells. PRDM16 is involved in human leukemic translocations and is expressed highly in some karyotypically normal acute myeloblastic leukemias. As many genes involved in leukemogenic fusions play a role in normal hematopoiesis, we analyzed the role of Prdm16 in the biology of HSCs using Prdm16-deficient mice. We show here that, within the hematopoietic system, Prdm16 is expressed very selectively in the earliest stem and progenitor compartments, and, consistent with this expression pattern, is critical for the establishment and maintenance of the HSC pool during development and after transplantation. Prdm16 deletion enhances apoptosis and cycling of HSCs. Expression analysis revealed that Prdm16 regulates a remarkable number of genes that, based on knockout models, both enhance and suppress HSC function, and affect quiescence, cell cycling, renewal, differentiation, and apoptosis to various extents. These data suggest that Prdm16 may be a critical node in a network that contains negative and positive feedback loops and integrates HSC renewal, quiescence, apoptosis, and differentiation.
ISSN:0006-4971
1528-0020
1528-0020
DOI:10.1182/blood-2010-08-300145