CD44 transmembrane receptor and hyaluronan regulate adult hippocampal neural stem cell quiescence and differentiation

Weiping Su, Scott C. Foster, Rubing Xing, Kerstin Feistel, Reid H J Olsen, Summer F. Acevedo, Jacob Raber, Larry S. Sherman

Research output: Research - peer-reviewArticle

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Abstract

Adult neurogenesis in the hippocampal subgranular zone (SGZ) is involved in learning and memory throughout life but declines with aging. Mice lacking the CD44 transmembrane receptor for the glycosaminoglycan hyaluronan (HA) demonstrate a number of neurological disturbances including hippocampal memory deficits, implicating CD44 in the processes underlying hippocampal memory encoding, storage, or retrieval. Here, we found that HA and CD44 play important roles in regulating adult neurogenesis, and we provide evidence that HA contributes to age-related reductions in neural stem cell (NSC) expansion and differentiation in the hippocampus. CD44-expressing NSCs isolated from the mouse SGZ are self-renewing and capable of differentiating into neurons, astrocytes, and oligodendrocytes. Mice lacking CD44 demonstrate increases in NSC proliferation in the SGZ. This increased proliferation is also observed in NSCs grown in vitro, suggesting that CD44 functions to regulate NSC proliferation in a cell-autonomous manner. HA is synthesized by NSCs and increases in the SGZ with aging. Treating wild type but not CD44-null NSCs with HA inhibits NSC proliferation. HA digestion in wild type NSC cultures or in the SGZ induces increased NSC proliferation, and CD44-null as well as HA-disrupted wild type NSCs demonstrate delayed neuronal differentiation. HA therefore signals through CD44 to regulate NSC quiescence and differentiation, and HA accumulation in the SGZ may contribute to reductions in neurogenesis that are linked to age-related decline in spatial memory.

LanguageEnglish (US)
Pages4434-4445
Number of pages12
JournalJournal of Biological Chemistry
Volume292
Issue number11
DOIs
StatePublished - Mar 17 2017

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CD44 Antigens
Neural Stem Cells
Hyaluronic Acid
Cell Differentiation
Stem cells
Cell Proliferation
Cell proliferation
Data storage equipment
Neurogenesis
Aging of materials
Oligodendroglia
Memory Disorders
Astrocytes
Digestion
Hippocampus
Cell Culture Techniques
Learning
Neurons
Spatial Memory
glycosaminoglycan receptor

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

CD44 transmembrane receptor and hyaluronan regulate adult hippocampal neural stem cell quiescence and differentiation. / Su, Weiping; Foster, Scott C.; Xing, Rubing; Feistel, Kerstin; Olsen, Reid H J; Acevedo, Summer F.; Raber, Jacob; Sherman, Larry S.

In: Journal of Biological Chemistry, Vol. 292, No. 11, 17.03.2017, p. 4434-4445.

Research output: Research - peer-reviewArticle

Su W, Foster SC, Xing R, Feistel K, Olsen RHJ, Acevedo SF et al. CD44 transmembrane receptor and hyaluronan regulate adult hippocampal neural stem cell quiescence and differentiation. Journal of Biological Chemistry. 2017 Mar 17;292(11):4434-4445. Available from, DOI: 10.1074/jbc.M116.774109
Su, Weiping ; Foster, Scott C. ; Xing, Rubing ; Feistel, Kerstin ; Olsen, Reid H J ; Acevedo, Summer F. ; Raber, Jacob ; Sherman, Larry S./ CD44 transmembrane receptor and hyaluronan regulate adult hippocampal neural stem cell quiescence and differentiation. In: Journal of Biological Chemistry. 2017 ; Vol. 292, No. 11. pp. 4434-4445
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