title: Transcriptome-wide profiling and posttranscriptional analysis of hematopoietic stem/progenitor cell differentiation toward myeloid commitment.
abstract: Hematopoietic stem cells possess lifelong self-renewal activity and generate multipotent progenitors that differentiate into lineage-committed and subsequently mature cells. We present a comparative transcriptome analysis of ex vivo isolated mouse multipotent hematopoietic stem/progenitor cells (Lin(neg)SCA-1(+)c-KIT(+)) and myeloid committed precursors (Lin(neg)SCA-1(neg)c-KIT(+)). Our data display dynamic transcriptional networks and identify a stem/progenitor gene expression pattern that is characterized by cell adhesion and immune response components including kallikrein-related proteases. We identify 498 expressed lncRNAs, which are potential regulators of multipotency or lineage commitment. By integrating these transcriptome with our recently reported proteome data, we found evidence for posttranscriptional regulation of processes including metabolism and response to oxidative stress. Finally, our study identifies a high number of genes with transcript isoform regulation upon lineage commitment. This in-depth molecular analysis outlines the enormous complexity of expressed coding and noncoding RNAs and posttranscriptional regulation during the early differentiation steps of hematopoietic stem cells toward the myeloid lineage.
authors.affiliation: Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ), 69120 Heidelberg, Germany; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120 Heidelberg, Germany; European Molecular Biology Laboratory (EMBL), Genome Biology Unit, 69120 Heidelberg, Germany; German Cancer Consortium (DKTK).
authors.forename: Daniel
authors.initials: D
authors.lastname: Klimmeck
authors.affiliation: Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ), 69120 Heidelberg, Germany; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120 Heidelberg, Germany; German Cancer Consortium (DKTK).
authors.forename: Nina
authors.initials: N
authors.lastname: Cabezas-Wallscheid
authors.affiliation: European Molecular Biology Laboratory (EMBL), Genome Biology Unit, 69120 Heidelberg, Germany.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Reyes
authors.affiliation: Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ), 69120 Heidelberg, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: von Paleske
authors.affiliation: Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ), 69120 Heidelberg, Germany; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120 Heidelberg, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Renders
authors.affiliation: European Molecular Biology Laboratory (EMBL), Genome Biology Unit, 69120 Heidelberg, Germany.
authors.forename: Jenny
authors.initials: J
authors.lastname: Hansson
authors.affiliation: European Molecular Biology Laboratory (EMBL), Genome Biology Unit, 69120 Heidelberg, Germany.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Krijgsveld
authors.affiliation: European Molecular Biology Laboratory (EMBL), Genome Biology Unit, 69120 Heidelberg, Germany. Electronic address: wolfgang.huber@embl.de.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Huber
authors.affiliation: Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ), 69120 Heidelberg, Germany; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120 Heidelberg, Germany; German Cancer Consortium (DKTK). Electronic address: a.trumpp@dkfz.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Trumpp
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics; D004734:Energy Metabolism / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D007109:Immunity / Q000235:genetics; D008810:Mice, Inbred C57BL; D039902:Multipotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D022423:Myeloid Cells / Q000166:cytology / Q000378:metabolism*; D020543:Proteome / Q000235:genetics / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D020543:Proteome; D062085:RNA, Long Noncoding