title: Human foreskin fibroblast produces interleukin-6 to support derivation and self-renewal of mouse embryonic stem cells.
abstract: BACKGROUND
  Embryonic stem cells (ESCs) provide an attractive cell source for basic research and disease treatment. Currently, the common culture system for mouse ESC requires mouse embryonic fibroblast (MEF) as a feeder layer supplemented with leukemia inhibitory factor (LIF). The drawbacks associated with MEF and the cost of LIF have motivated exploration of new feeder cell types to maintain self-renewal of mouse ESCs without the need of exogenous LIF. However, why these feeder cells could maintain ESCs at the undifferentiated state independent of exogenous LIF is unclear.
  
  
  METHODS
  We derived mouse ESC lines using human foreskin fibroblast (HFF) in the absence of exogenous LIF. We also examined the dependence of HFF on the JAK-Stat3 pathway to maintain ESC identities and explored the potential molecular basis for HFF to support self-renewal of ESCs.
  
  
  RESULTS
  HFF supported mouse ESC self-renewal superiorly to MEFs. Using the HFF system, multiple lines of mouse ESCs were successfully derived without addition of exogenous LIF and any small molecular inhibitors. These ESCs had capacities to self-renew for a long period of time and to differentiate into various cell types of the three germ layers both in vitro and in vivo. Moreover, the ESCs participated in embryonic development and contributed to germ cell lineages in the chimeric mouse. At a molecular level, HFF was dependent on the JAK-Stat3 pathway to maintain ESC self-renewal. The high level of interleukin-6 (IL-6) produced by HFF might be responsible for the exogenous LIF-independent effect.
  
  
  CONCLUSIONS
  This study describes an efficient, convenient and economic system to establish and maintain mouse ESC lines, and provides insights into the functional difference in the support of ESC culture between MEF and HFF.
authors: Yu
authors: Y
authors: Ma
authors: Junjie
authors: J
authors: Gu
authors: Chunliang
authors: C
authors: Li
authors: Xiaoyuan
authors: X
authors: Wei
authors: Fan
authors: F
authors: Tang
authors: Guilai
authors: G
authors: Shi
authors: Jing
authors: J
authors: Jiang
authors: Ying
authors: Y
authors: Kuang
authors: Jinsong
authors: J
authors: Li
authors: Zhugang
authors: Z
authors: Wang
authors: Xin
authors: X
authors: Xie
authors: Ying
authors: Y
authors: Jin
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology; D053595:Embryonic Stem Cells / Q000166:cytology*; D061252:Feeder Cells / Q000166:cytology / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D052816:Foreskin / Q000166:cytology*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D053612:Janus Kinases / Q000378:metabolism; D053605:Leukemia Inhibitory Factor / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D050796:STAT3 Transcription Factor; D053612:Janus Kinases