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Fine‐tuning Nanog expression heterogeneity in embryonic stem cells by regulating a Nanog transcript‐specific microRNA
Author(s) -
Samanta Tagari,
Kar Sandip
Publication year - 2020
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13936
Subject(s) - homeobox protein nanog , embryonic stem cell , microrna , rex1 , biology , microbiology and biotechnology , nanog homeobox protein , transcription factor , regulation of gene expression , cellular differentiation , stem cell , genetics , gene , induced pluripotent stem cell
In embryonic stem cells (ESCs), the transcription factor Nanog maintains the stemness of ESCs despite exhibiting heterogeneous expression patterns under varied culture conditions. Efficient fine‐tuning of Nanog expression heterogeneity could enable ESC proliferation and differentiation along specific lineages to be regulated. Herein, by employing a stochastic modeling approach, we show that Nanog expression heterogeneity can be controlled by modulating the regulatory features of a Nanog transcript‐specific microRNA, mir‐296. We demonstrate how and why the extent of origin‐dependent fluctuations in Nanog expression level can be altered by varying either the binding efficiency of the microRNA–mRNA complex or the expression level of mir‐296. Moreover, our model makes experimentally feasible and insightful predictions to maneuver Nanog expression heterogeneity explicitly to achieve cell‐type‐specific differentiation of ESCs.