Cell type-specific expression profile and signaling requirements in early hematopoietic reprogramming

Stem Cells Dev. 2015 Jun 15;24(12):1483-92. doi: 10.1089/scd.2014.0422. Epub 2015 Apr 6.

Abstract

Hematopoietic cells represent an attractive starting cell type for induced pluripotent stem (iPS) cells induction, yet the molecular mechanisms in hematopoietic reprogramming are poorly defined. In this study, we showed that long-term hematopoietic stem cells are more amenable for iPS cells induction among several hematopoietic stem and progenitor cell (HSPC) populations, and that this is accompanied by an earlier induction of the transcriptional program that is involved in the promotion of macromolecule metabolism and cell proliferation. Notably, we identified multiple signaling pathways that exhibited distinct expression patterns in HSPCs compared to that of fibroblasts, which is the most commonly used model for probing the somatic reprogramming process. We further experimentally confirmed the differential requirements of the Wnt/β-catenin and transforming growth factor-beta (TGF-β) signaling pathways in these two cell types. These data demonstrate that hematopoietic cells have a cell-type specific transcriptional program and possess unique signaling requirements in the early phase of reprogramming.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / genetics*
  • Cell Lineage / genetics
  • Cellular Reprogramming / genetics*
  • Fibroblasts / metabolism
  • Gene Expression Regulation, Developmental
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism*
  • Humans
  • Induced Pluripotent Stem Cells / metabolism*
  • Induced Pluripotent Stem Cells / pathology
  • Transcriptome
  • Transforming Growth Factor beta / genetics
  • Wnt Signaling Pathway / genetics

Substances

  • Transforming Growth Factor beta