title: Distinct Molecular Signature of Murine Fetal Liver and Adult Hematopoietic Stem Cells Identify Novel Regulators of Hematopoietic Stem Cell Function.
abstract: During ontogeny, fetal liver (FL) acts as a major site for hematopoietic stem cell (HSC) maturation and expansion, whereas HSCs in the adult bone marrow (ABM) are largely quiescent. HSCs in the FL possess faster repopulation capacity as compared with ABM HSCs. However, the molecular mechanism regulating the greater self-renewal potential of FL HSCs has not yet extensively been assessed. Recently, we published RNA sequencing-based gene expression analysis on FL HSCs from 14.5-day mouse embryo (E14.5) in comparison to the ABM HSCs. We reanalyzed these data to identify key transcriptional regulators that play important roles in the expansion of HSCs during development. The comparison of FL E14.5 with ABM HSCs identified more than 1,400 differentially expressed genes. More than 200 genes were shortlisted based on the gene ontology (GO) annotation term "transcription." By morpholino-based knockdown studies in zebrafish, we assessed the function of 18 of these regulators, previously not associated with HSC proliferation. Our studies identified a previously unknown role for tdg, uhrf1, uchl5, and ncoa1 in the emergence of definitive hematopoiesis in zebrafish. In conclusion, we demonstrate that identification of genes involved in transcriptional regulation differentially expressed between expanding FL HSCs and quiescent ABM HSCs, uncovers novel regulators of HSC function.
authors.affiliation: 1 Inter-Departmental Stem Cell Institute, KU Leuven , Leuven, Belgium .|2 Department of Development and Regeneration, Stem Cell Biology and Embryology, KU Leuven , Leuven, Belgium .
authors.forename: Javed K
authors.initials: JK
authors.lastname: Manesia
authors.affiliation: 3 Functional Bioinformatics Group, National Center for Biotechnology-CSIC , Madrid, Spain .
authors.forename: Monica
authors.initials: M
authors.lastname: Franch
authors.affiliation: 3 Functional Bioinformatics Group, National Center for Biotechnology-CSIC , Madrid, Spain .
authors.forename: Daniel
authors.initials: D
authors.lastname: Tabas-Madrid
authors.affiliation: 3 Functional Bioinformatics Group, National Center for Biotechnology-CSIC , Madrid, Spain .
authors.forename: Ruben
authors.initials: R
authors.lastname: Nogales-Cadenas
authors.affiliation: 1 Inter-Departmental Stem Cell Institute, KU Leuven , Leuven, Belgium .|2 Department of Development and Regeneration, Stem Cell Biology and Embryology, KU Leuven , Leuven, Belgium .
authors.forename: Thomas
authors.initials: T
authors.lastname: Vanwelden
authors.affiliation: 1 Inter-Departmental Stem Cell Institute, KU Leuven , Leuven, Belgium .|2 Department of Development and Regeneration, Stem Cell Biology and Embryology, KU Leuven , Leuven, Belgium .
authors.forename: Elisa
authors.initials: E
authors.lastname: Van Den Bosch
authors.affiliation: 1 Inter-Departmental Stem Cell Institute, KU Leuven , Leuven, Belgium .|2 Department of Development and Regeneration, Stem Cell Biology and Embryology, KU Leuven , Leuven, Belgium .
authors.forename: Zhuofei
authors.initials: Z
authors.lastname: Xu
authors.affiliation: 3 Functional Bioinformatics Group, National Center for Biotechnology-CSIC , Madrid, Spain .
authors.forename: Alberto
authors.initials: A
authors.lastname: Pascual-Montano
authors.affiliation: 1 Inter-Departmental Stem Cell Institute, KU Leuven , Leuven, Belgium .|2 Department of Development and Regeneration, Stem Cell Biology and Embryology, KU Leuven , Leuven, Belgium .|4 Indian Institute of Science Education and Research , Thiruvananthapuram, India .
authors.forename: Satish
authors.initials: S
authors.lastname: Khurana
authors.affiliation: 1 Inter-Departmental Stem Cell Institute, KU Leuven , Leuven, Belgium .|2 Department of Development and Regeneration, Stem Cell Biology and Embryology, KU Leuven , Leuven, Belgium .
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Verfaillie
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006410:Hematopoiesis / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D008099:Liver / Q000166:cytology* / Q000196:embryology; D051379:Mice; D008810:Mice, Inbred C57BL; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D014157:Transcription Factors; D029961:Zebrafish Proteins
keywords: HSC; hematopoiesis; zebrafish