Identification of Three Early Phases of Cell-Fate Determination during Osteogenic and Adipogenic Differentiation by Transcription Factor Dynamics

Jeroen van de Peppel, Tanja Strini, Julia Tilburg, Hans Westerhoff, Andre J van Wijnen, Johannes P. van Leeuwen

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Age-related skeletal degeneration in patients with osteoporosis is characterized by decreased bone mass and occurs concomitant with an increase in bone marrow adipocytes. Using microarray expression profiling with high temporal resolution, we identified gene regulatory events in early stages of osteogenic and adipogenic lineage commitment of human mesenchymal stromal cells (hMSCs). Data analysis revealed three distinct phases when cells adopt a committed expression phenotype: initiation of differentiation (0-3 hr, phase I), lineage acquisition (6-24 hr, phase II), and early lineage progression (48-96 hr, phase III). Upstream regulator analysis identified 34 transcription factors (TFs) in phase I with a role in hMSC differentiation. Interestingly, expression levels of identified TFs did not always change and indicate additional post-transcriptional regulatory mechanisms. Functional analysis revealed that forced expression of IRF2 enhances osteogenic differentiation. Thus, IRF2 and other early-responder TFs may control osteogenic cell fate of MSCs and should be considered in mechanistic models that clarify bone-anabolic changes during clinical progression of osteoporosis. In this article, van Leeuwen and colleagues determine high temporal gene expression changes in human mesenchymal stromal cells upon induction of adipocyte and osteoblast differentiation. They identify three early differentiation phases within the first 4 days. Furthermore, novel transcription factors were identified that may control cell fate of hMSCs and should be considered in mechanistic models that clarify bone-anabolic changes.

Original languageEnglish (US)
JournalStem Cell Reports
DOIs
StateAccepted/In press - Jun 9 2016

Fingerprint

Mesenchymal Stromal Cells
Bone
Transcription Factors
Adipocytes
Bone and Bones
Osteoporosis
Functional analysis
Osteoblasts
Regulator Genes
Microarrays
Gene expression
Cell Differentiation
Genes
Bone Marrow
Phenotype
Gene Expression

Keywords

  • Adipocyte
  • Bioinformatics
  • Bone
  • Gene expression profiling
  • Human MSC differentiation
  • Interferon
  • Osteoblast
  • Regenerative medicine
  • Transcription factor

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

Cite this

Identification of Three Early Phases of Cell-Fate Determination during Osteogenic and Adipogenic Differentiation by Transcription Factor Dynamics. / van de Peppel, Jeroen; Strini, Tanja; Tilburg, Julia; Westerhoff, Hans; van Wijnen, Andre J; van Leeuwen, Johannes P.

In: Stem Cell Reports, 09.06.2016.

Research output: Contribution to journalArticle

van de Peppel, Jeroen ; Strini, Tanja ; Tilburg, Julia ; Westerhoff, Hans ; van Wijnen, Andre J ; van Leeuwen, Johannes P. / Identification of Three Early Phases of Cell-Fate Determination during Osteogenic and Adipogenic Differentiation by Transcription Factor Dynamics. In: Stem Cell Reports. 2016.
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