title: Prdm16 is a physiologic regulator of hematopoietic stem cells.
abstract: 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.
authors.affiliation: Department of Gene and Cell Medicine and Black Family Stem Cell Institute, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Francesca
authors.initials: F
authors.lastname: Aguilo
authors.forename: Serine
authors.initials: S
authors.lastname: Avagyan
authors.forename: Amy
authors.initials: A
authors.lastname: Labar
authors.forename: Ana
authors.initials: A
authors.lastname: Sevilla
authors.forename: Dung-Fang
authors.initials: DF
authors.lastname: Lee
authors.forename: Parameet
authors.initials: P
authors.lastname: Kumar
authors.forename: Ihor R
authors.initials: IR
authors.lastname: Lemischka
authors.forename: Betty Y
authors.initials: BY
authors.lastname: Zhou
authors.forename: Hans-Willem
authors.initials: HW
authors.lastname: Snoeck
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D002469:Cell Separation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D015870:Gene Expression; D020869:Gene Expression Profiling; D005838:Genotype; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C521133:Prdm16 protein, mouse; D014157:Transcription Factors