title: NF-Y is necessary for hematopoietic stem cell proliferation and survival.
abstract: HSC function depends on the tight control of proliferation and the balance between self-renewal and differentiation. Here, we report that the trimeric transcription factor NF-Y is critical for the survival of cycling, but not quiescent HSCs. With the use of a conditional knockout mouse model, we demonstrate that NF-Ya deletion creates an accumulation of HSCs in G(2)/M and prompts apoptosis, causing hematopoietic failure and death of the animal. These defects are accompanied by the dysregulation of multiple genes that influence cell cycle control (cyclin b1 and p21), apoptosis (Bcl-2), and self-renewal (HoxB4, Notch1, Bmi-1) and are independent of p53. Our results identify NF-Y as a pivotal upstream participant in a regulatory network necessary for the preservation of cycling HSCs.
authors.affiliation: Division of Hematology/Oncology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: Gerd
authors.initials: G
authors.lastname: Bungartz
authors.forename: Hannah
authors.initials: H
authors.lastname: Land
authors.forename: David T
authors.initials: DT
authors.lastname: Scadden
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Emerson
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000378:metabolism; D023081:CCAAT-Binding Factor / Q000235:genetics* / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D006410:Hematopoiesis / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D063150:Polycomb Repressive Complex 1; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D060168:Thymocytes / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: C489421:Bmi1 protein, mouse; D023081:CCAAT-Binding Factor; D018797:Cell Cycle Proteins; D018398:Homeodomain Proteins; C513262:Hoxb4 protein, mouse; C492060:Nfya protein, mouse; C497762:Notch1 protein, mouse; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D051881:Receptor, Notch1; D012097:Repressor Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D063150:Polycomb Repressive Complex 1
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