TY - JOUR
T1 - Nuclear reprogramming strategy modulates differentiation potential of induced pluripotent stem cells
AU - Martinez-Fernandez, Almudena
AU - Nelson, Timothy J.
AU - Terzic, Andre
N1 - Funding Information:
Acknowledgments Work in the laboratory of the authors was supported by the National Institutes of Health, Marriott Individualized Medicine Program, Marriott Heart Disease Research Program, and Mayo Clinic.
PY - 2011/4
Y1 - 2011/4
N2 - Bioengineered by ectopic expression of stemness factors, induced pluripotent stem (iPS) cells demonstrate embryonic stemcell-like properties and offer a unique platform for derivation of autologous pluripotent cells from somatic tissue sources. In the process of nuclear reprogramming, somatic tissues are converted to a pluripotent ground state, thus unlocking an unlimited potential to expand progenitor pools. Molecular dissection of nuclear reprogramming suggests that a residual memory derived from the original parental source, along with the remnants of the reprogramming process itself, leads to a biased potential of the bioengineered progeny to differentiate into target tissues such as cardiac cytotypes. In this way, iPS cells that fulfill pluripotency criteria may display heterogeneous profiles for lineage specification. Small molecule-based strategies have been identified that modulate the epigenetic state of reprogrammed cells and are optimized to erase the residual memory and homogenize the differentiation potential of iPS cells derived from distinct backgrounds. Here, we describe the salient components of the reprogramming process and their effect on the downstream differentiation capacity of the iPS populations in the context of cardiovascular regenerative applications.
AB - Bioengineered by ectopic expression of stemness factors, induced pluripotent stem (iPS) cells demonstrate embryonic stemcell-like properties and offer a unique platform for derivation of autologous pluripotent cells from somatic tissue sources. In the process of nuclear reprogramming, somatic tissues are converted to a pluripotent ground state, thus unlocking an unlimited potential to expand progenitor pools. Molecular dissection of nuclear reprogramming suggests that a residual memory derived from the original parental source, along with the remnants of the reprogramming process itself, leads to a biased potential of the bioengineered progeny to differentiate into target tissues such as cardiac cytotypes. In this way, iPS cells that fulfill pluripotency criteria may display heterogeneous profiles for lineage specification. Small molecule-based strategies have been identified that modulate the epigenetic state of reprogrammed cells and are optimized to erase the residual memory and homogenize the differentiation potential of iPS cells derived from distinct backgrounds. Here, we describe the salient components of the reprogramming process and their effect on the downstream differentiation capacity of the iPS populations in the context of cardiovascular regenerative applications.
KW - Differentiation capacity
KW - Epigenetic memory
KW - Memory-free pluripotency
KW - iPS
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U2 - 10.1007/s12265-010-9250-2
DO - 10.1007/s12265-010-9250-2
M3 - Article
C2 - 21207217
AN - SCOPUS:79956367028
SN - 1937-5387
VL - 4
SP - 131
EP - 137
JO - Journal of cardiovascular translational research
JF - Journal of cardiovascular translational research
IS - 2
ER -