title: C/EBPa controls acquisition and maintenance of adult haematopoietic stem cell quiescence.
abstract: In blood, the transcription factor C/EBPa is essential for myeloid differentiation and has been implicated in regulating self-renewal of fetal liver haematopoietic stem cells (HSCs). However, its function in adult HSCs has remained unknown. Here, using an inducible knockout model we found that C/EBPa-deficient adult HSCs underwent a pronounced increase in number with enhanced proliferation, characteristics resembling fetal liver HSCs. Consistently, transcription profiling of C/EBPa-deficient HSCs revealed a gene expression program similar to fetal liver HSCs. Moreover, we observed that age-specific Cebpa expression correlated with its inhibitory effect on the HSC cell cycle. Mechanistically we identified N-Myc as a downstream target of C/EBPa, and loss of C/EBPa resulted in de-repression of N-Myc. Our data establish C/EBPa as a central determinant in the switch from fetal to adult HSCs.
authors.affiliation: Harvard Stem Cell Institute, Harvard Medical School, and Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Ye
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Giovanni
authors.initials: G
authors.lastname: Amabile
authors.forename: Henry
authors.initials: H
authors.lastname: Yang
authors.forename: Philipp B
authors.initials: PB
authors.lastname: Staber
authors.forename: Pu
authors.initials: P
authors.lastname: Zhang
authors.forename: Elena
authors.initials: E
authors.lastname: Levantini
authors.forename: Meritxell
authors.initials: M
authors.lastname: Alberich-Jordà
authors.forename: Junyan
authors.initials: J
authors.lastname: Zhang
authors.forename: Akira
authors.initials: A
authors.lastname: Kawasaki
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Tenen
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology* / Q000502:physiology; D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D016026:Bone Marrow Transplantation; D022762:CCAAT-Enhancer-Binding Proteins / Q000502:physiology*; D002453:Cell Cycle; D002454:Cell Differentiation; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D053686:Fetal Stem Cells / Q000166:cytology* / Q000502:physiology; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology; D019426:Integrases / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D022762:CCAAT-Enhancer-Binding Proteins; C530718:CEBPA protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D008156:Luciferases; C045073:Cre recombinase; D019426:Integrases