Premium
Gap junctional intercellular communication is required to maintain embryonic stem cells in a non‐differentiated and proliferative state
Author(s) -
Todorova Mariana G.,
Soria Bernat,
Quesada Ivan
Publication year - 2008
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.21203
Subject(s) - embryonic stem cell , microbiology and biotechnology , embryoid body , homeobox protein nanog , induced pluripotent stem cell , biology , intracellular , stem cell , gap junction , cellular differentiation , fluorescence recovery after photobleaching , biochemistry , membrane , gene
Pluripotent embryonic stem (ES) cells are capable of maintaining a self‐renewal state and have the potential to differentiate into derivatives of all three embryonic germ layers. Despite their importance in cell therapy and developmental biology, the mechanisms whereby ES cells remain in a proliferative and pluripotent state are still not fully understood. Here we establish a critical role of gap junctional intercellular communication (GJIC) and connexin43 (Cx43) in both processes. Pharmacological blockers of GJIC and Cx43 down‐regulation by small interfering RNA (siRNA) caused a profound inhibitory effect on GJIC, as evidenced by experiments of fluorescence recovery after photobleaching. This deficient intercellular communication in ES cells induced a loss of their pluripotent state, which was manifested in morphological changes, a decrease in alkaline phosphatase activity, Oct‐3/4 and Nanog expression, as well as an up‐regulation of several differentiation markers. A decrease in the proliferation rate was also detected. Under these conditions, the formation of embryoid bodies from mouse ES cells was impaired, although this inhibition was reversible upon restoration of GJIC. Our findings define a major function of GJIC in the regulation of self‐renewal and maintenance of pluripotency in ES cells. J. Cell. Physiol. 214: 354–362, 2008. © 2007 Wiley‐Liss, Inc.