Transcriptome-wide profiling and posttranscriptional analysis of hematopoietic stem/progenitor cell differentiation toward myeloid commitment

Research output: Contribution to journalArticle

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.

Details

Authors
  • Daniel Klimmeck
  • Nina Cabezas-Wallscheid
  • Alejandro Reyes
  • Lisa von Paleske
  • Simon Renders
  • Jenny Hansson
  • Jeroen Krijgsveld
  • Wolfgang Huber
  • Andreas Trumpp
Organisations
External organisations
  • European Molecular Biology Laboratory Heidelberg
Research areas and keywords

Keywords

  • Animals, Cell Adhesion, Cell Cycle, Cell Differentiation, Cell Lineage, Energy Metabolism, Female, Flow Cytometry, Gene Expression Profiling, Gene Ontology, Gene Regulatory Networks, Hematopoietic Stem Cells, Immunity, Mice, Inbred C57BL, Multipotent Stem Cells, Myeloid Cells, Proteome, RNA, Long Noncoding, Reverse Transcriptase Polymerase Chain Reaction
Original languageEnglish
Pages (from-to)858-75
Number of pages18
JournalStem Cell Reports
Volume3
Issue number5
Publication statusPublished - 2014 Nov 11
Publication categoryResearch
Peer-reviewedYes