title: Maintenance of the self-renewal properties of neural progenitor cells cultured in three-dimensional collagen scaffolds by the REDD1-mTOR signal pathway.
abstract: Three-dimensional (3-D) culture, compared with traditional two-dimensional (2-D) cell culture, can provide physical signals and 3-D matrix close to the in vivo microenvironments. Here, sponge-like collagen scaffolds were used to assess how 3-D culture would affect the differentiation and self-renewal of neural progenitor cells (NPCs). Cultured in differentiation medium without growth factors, cells in 3-D collagen scaffolds yielded much higher clone formation efficiency and expressed less neuron marker, TUJ1, compared with cells cultured on 2-D plates. mTOR inactivation was identified and showed to supported the self-renewal of NPCs in 3-D culture. At the same time, REDD1 was highly expressed in cells cultured in 3-D conditions, which blocks the activity of mTOR. Moreover, knocking-down REDD1 induced the differentiation of NPCs in 3-D collagen scaffolds. These results indicated that mTOR inactivation by REDD1 mediated the self-renewal regulation of NPCs in 3-D cultures. Thus, 3-D collagen scaffolds maintained self-renewal properties of NPCs, and the inhibitory regulator of mTOR (such as REDD1) played an important role in the regulation of self-renewal and differentiation of NPCs.
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Han
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Xiao
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Bing
authors.initials: B
authors.lastname: Chen
authors.forename: Xiaoran
authors.initials: X
authors.lastname: Li
authors.forename: Sufang
authors.initials: S
authors.lastname: Han
authors.forename: Yannan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Jianwu
authors.initials: J
authors.lastname: Dai
mesh_terms: D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology*; D003114:Colony-Forming Units Assay; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*; D014157:Transcription Factors; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C000632146:Ddit4 protein, rat; D012097:Repressor Proteins; D014157:Transcription Factors; D003094:Collagen; D058570:TOR Serine-Threonine Kinases