TY - JOUR
T1 - The cell cycle- and insulin-signaling-inhibiting miRNA expression pattern of very small embryonic-like stem cells contributes to their quiescent state
AU - Maj, Magdalena
AU - Schneider, Gabriela
AU - Ratajczak, Janina
AU - Suszynska, Malwina
AU - Kucia, Magda
AU - Ratajczak, Mariusz Z.
N1 - Funding Information:
This work was supported by NIH grants 2R01 DK074720 and R01HL112788 and the Stella and Henry Endowment to MZR.
Publisher Copyright:
© 2015, © 2015 by the Society for Experimental Biology and Medicine.
PY - 2015/8/19
Y1 - 2015/8/19
N2 - Murine Oct4+, very small embryonic-like stem cells (VSELs), are a quiescent stem cell population that requires a supportive co-culture layer to proliferate and/or to differentiate in vitro. Gene expression studies have revealed that the quiescence of these cells is due to changes in expression of parentally imprinted genes, including genes involved in cell cycle regulation and insulin and insulin-like growth factor signaling (IIS). To investigate the role of microRNAs (miRNAs) in VSEL quiescence, we performed miRNA studies in highly purified VSELs and observed a unique miRNA expression pattern in these cells. Specifically, we observed significant differences in the expression of certain miRNA species (relative to a reference cell population), including (i) miRNA-25_1 and miRNA-19 b, whose downregulation has the effect of upregulating cell cycle checkpoint genes and (ii) miRNA-675-3 p and miRNA-675-5 p, miRNA-292-5 p, miRNA-184, and miRNA-125 b, whose upregulation attenuates IIS. These observations are important for understanding the biology of these cells and for developing efficient ex vivo expansion strategies for VSELs isolated from adult tissues.
AB - Murine Oct4+, very small embryonic-like stem cells (VSELs), are a quiescent stem cell population that requires a supportive co-culture layer to proliferate and/or to differentiate in vitro. Gene expression studies have revealed that the quiescence of these cells is due to changes in expression of parentally imprinted genes, including genes involved in cell cycle regulation and insulin and insulin-like growth factor signaling (IIS). To investigate the role of microRNAs (miRNAs) in VSEL quiescence, we performed miRNA studies in highly purified VSELs and observed a unique miRNA expression pattern in these cells. Specifically, we observed significant differences in the expression of certain miRNA species (relative to a reference cell population), including (i) miRNA-25_1 and miRNA-19 b, whose downregulation has the effect of upregulating cell cycle checkpoint genes and (ii) miRNA-675-3 p and miRNA-675-5 p, miRNA-292-5 p, miRNA-184, and miRNA-125 b, whose upregulation attenuates IIS. These observations are important for understanding the biology of these cells and for developing efficient ex vivo expansion strategies for VSELs isolated from adult tissues.
KW - MicroRNA
KW - insulin/insulin-like growth factor signaling
KW - p57
KW - quiescence
KW - very small embryonic-like stem cells
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U2 - 10.1177/1535370215584940
DO - 10.1177/1535370215584940
M3 - Article
C2 - 25966979
AN - SCOPUS:84939484736
SN - 1535-3702
VL - 240
SP - 1107
EP - 1111
JO - Experimental Biology and Medicine
JF - Experimental Biology and Medicine
IS - 8
ER -