TGF-β1 Negatively Regulates the Number and Function of Hematopoietic Stem Cells

Stem Cell Reports. 2018 Jul 10;11(1):274-287. doi: 10.1016/j.stemcr.2018.05.017. Epub 2018 Jun 21.

Abstract

Transforming growth factor β1 (TGF-β1) plays a role in the maintenance of quiescent hematopoietic stem cells (HSCs) in vivo. We asked whether TGF-β1 controls the cell cycle status of HSCs in vitro to enhance the reconstitution activity. To examine the effect of TGF-β1 on the HSC function, we used an in vitro culture system in which single HSCs divide with the retention of their short- and long-term reconstitution ability. Extensive single-cell analyses showed that, regardless of its concentration, TGF-β1 slowed down the cell cycle progression of HSCs but consequently suppressed their self-renewal potential. Cycling HSCs were not able to go back to quiescence with TGF-β1. This study revealed a negative role of TGF-β1 in the regulation of the HSC number and reconstitution activity.

Keywords: G0 phase; apoptosis; cell cycle; differentiation; hematopoietic stem cells; quiescence; self-renewal; transforming growth factor β1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Cycle
  • Cell Differentiation
  • Cell Division / genetics
  • Cell Self Renewal
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / metabolism*
  • Mice
  • Transforming Growth Factor beta1 / metabolism*

Substances

  • Transforming Growth Factor beta1