Effects of paracrine factors on CD24 expression and neural differentiation of male germline stem cells

Int J Mol Med. 2015 Jul;36(1):255-62. doi: 10.3892/ijmm.2015.2208. Epub 2015 May 12.

Abstract

Spermatogonial stem cells (SSCs) are adult male germ cells that develop after birth. Throughout the lifetime of an organism, SSCs sustain spermatogenesis through self-renewal and produce daughter cells that differentiate into spermatozoa. Several studies have demonstrated that SSCs can acquire pluripotency under appropriate culture conditions, thus becoming multipotent germline stem cells (mGSCs) that express markers of pluripotency in culture and form teratomas following transplantation into immunodeficient mice. In the present study, we generated neural precursor cells expressing CD24, a neural precursor marker, from pluripotent stem cell lines and demonstrated that these cells effectively differentiated along a neural lineage in vitro. In addition, we found that paracrine factors promoted CD24 expression during the neural differentiation of mGSCs. Our results indicated that the expression of CD24, enhanced by a combination of retinoic acid (RA), noggin and fibroblast growth factor 8 (FGF8) under serum-free conditions promoted neural precursor differentiation. Using a simple cell sorting method, we were able to collect neural precursor cells with the potential to differentiate from mGSCs into mature neurons and astrocytes in vitro.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / cytology*
  • Animals
  • Astrocytes / cytology
  • Bone Morphogenetic Protein 4 / pharmacology
  • CD24 Antigen / biosynthesis*
  • Carrier Proteins / pharmacology
  • Cells, Cultured
  • Fibroblast Growth Factor 8 / pharmacology
  • Fibroblasts
  • Glial Cell Line-Derived Neurotrophic Factor / pharmacology
  • Hedgehog Proteins / pharmacology
  • Intercellular Signaling Peptides and Proteins / pharmacology*
  • Male
  • Mice
  • Mice, Inbred CBA
  • Mice, Transgenic
  • Microtubule-Associated Proteins / metabolism
  • Neural Stem Cells / cytology
  • Neurogenesis / drug effects*
  • Neurons / cytology
  • Pluripotent Stem Cells / cytology*
  • Pluripotent Stem Cells / metabolism
  • Spermatogonia / cytology
  • Tretinoin / pharmacology

Substances

  • Bmp4 protein, mouse
  • Bone Morphogenetic Protein 4
  • CD24 Antigen
  • Carrier Proteins
  • Cd24a protein, mouse
  • Fgf8 protein, mouse
  • Glial Cell Line-Derived Neurotrophic Factor
  • Hedgehog Proteins
  • Intercellular Signaling Peptides and Proteins
  • Microtubule-Associated Proteins
  • Shh protein, mouse
  • noggin protein
  • Fibroblast Growth Factor 8
  • Tretinoin