PMID- 25537496
OWN - NLM
STAT- MEDLINE
DCOM- 20160115
LR  - 20211203
IS  - 1549-4918 (Electronic)
IS  - 1066-5099 (Linking)
VI  - 33
IP  - 4
DP  - 2015 Apr
TI  - Brief report: the differential roles of mTORC1 and mTORC2 in mesenchymal stem 
      cell differentiation.
PG  - 1359-65
LID - 10.1002/stem.1931 [doi]
AB  - Adipocytes (AdCs) and osteoblasts (OBs) are derived from mesenchymal stem cells 
      (MSCs) and differentiation toward either lineage is both mutually exclusive and 
      transcriptionally controlled. Recent studies implicate the mammalian target of 
      rapamycin (mTOR) pathway as important in determining MSC fate, with inhibition of 
      mTOR promoting OB differentiation and suppressing AdC differentiation. mTOR 
      functions within two distinct multiprotein complexes, mTORC1 and mTORC2, each of 
      which contains the unique adaptor protein, raptor or rictor, respectively. While 
      compounds used to study mTOR signaling, such as rapamycin and related analogs, 
      primarily inhibit mTORC1, prolonged exposure can also disrupt mTORC2 function, 
      confounding interpretation of inhibitor studies. As a result, the relative 
      contribution of mTORC1 and mTORC2 to MSC fate determination remains unclear. In 
      this study, we generated primary mouse MSCs deficient in either Rptor (RapKO) or 
      Rictor (RicKO) using the Cre/loxP system. Cre-mediated deletion of Rptor or 
      Rictor resulted in impaired mTORC1 and mTORC2 signaling, respectively. Under 
      lineage-inductive culture conditions, RapKO MSCs displayed a reduced capacity to 
      form lipid-laden AdCs and an increased capacity to form a mineralized matrix. In 
      contrast, RicKO MSCs displayed reduced osteogenic differentiation capacity and 
      enhanced adipogenic differentiation potential. Taken together, our findings 
      reveal distinct roles for mTORC1 and mTORC2 in MSC lineage commitment.
CI  - (c) 2014 AlphaMed Press.
FAU - Martin, Sally K
AU  - Martin SK
AD  - Myeloma Research Laboratory, School of Medical Sciences, University of Adelaide, 
      Adelaide, South Australia, Australia; Centre for Cancer Biology, SA Pathology, 
      Adelaide, South Australia, Australia; Centre for Stem Cell Research, University 
      of Adelaide, Adelaide, South Australia, Australia.
FAU - Fitter, Stephen
AU  - Fitter S
FAU - Dutta, Ankit K
AU  - Dutta AK
FAU - Matthews, Mary P
AU  - Matthews MP
FAU - Walkley, Carl R
AU  - Walkley CR
FAU - Hall, Michael N
AU  - Hall MN
FAU - Ruegg, Markus A
AU  - Ruegg MA
FAU - Gronthos, Stan
AU  - Gronthos S
FAU - Zannettino, Andrew C W
AU  - Zannettino AC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Stem Cells
JT  - Stem cells (Dayton, Ohio)
JID - 9304532
RN  - 0 (Multiprotein Complexes)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 2)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Cell Differentiation/*physiology
MH  - Cell Proliferation/physiology
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Mechanistic Target of Rapamycin Complex 2
MH  - Mesenchymal Stem Cells/*physiology
MH  - Mice
MH  - Mice, Knockout
MH  - Multiprotein Complexes/*physiology
MH  - TOR Serine-Threonine Kinases/*physiology
OTO - NOTNLM
OT  - Mesenchymal stem cell
OT  - Raptor
OT  - Rictor
OT  - mTOR
EDAT- 2014/12/30 06:00
MHDA- 2016/01/16 06:00
CRDT- 2014/12/25 06:00
PHST- 2014/09/29 00:00 [received]
PHST- 2014/11/12 00:00 [revised]
PHST- 2014/12/03 00:00 [accepted]
PHST- 2014/12/25 06:00 [entrez]
PHST- 2014/12/30 06:00 [pubmed]
PHST- 2016/01/16 06:00 [medline]
AID - 10.1002/stem.1931 [doi]
PST - ppublish
SO  - Stem Cells. 2015 Apr;33(4):1359-65. doi: 10.1002/stem.1931.