MicroRNAs are indispensable for reprogramming mouse embryonic fibroblasts into induced stem cell-like cells.
MicroRNAs play a pivotal role in cellular maintenance, proliferation, and differentiation. They have also been implicated to play a key role in disease pathogenesis, and more recently, cellular reprogramming. Certain microRNA clusters can enhance or even directly induce reprogramming, while repressing key proteins involved in microRNA processing decreases reprogramming efficiency. Although microRNAs clearly play important roles in cellular reprogramming, it remains unknown whether microRNAs are absolutely necessary. We endeavored to answer this fundamental question by attempting to reprogram Dicer-null mouse embryonic fibroblasts (MEFs) that lack almost all functional microRNAs using a defined set of transcription factors. Transduction of reprogramming factors using either lentiviral or piggyBac transposon vector into two, independently derived lines of Dicer-null MEFs failed to produce cells resembling embryonic stem cells (ESCs). However, expression of human Dicer in the Dicer-null MEFs restored their reprogramming potential. Our study demonstrates for the first time that microRNAs are indispensable for dedifferentiation reprogramming.
Department of Medicine/GI Unit, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
Byeong-Moo
BM
Kim
Marc-Christian
MC
Thier
Sangnam
S
Oh
Richard
R
Sherwood
Chryssa
C
Kanellopoulou
Frank
F
Edenhofer
Michael Y
MY
Choi
D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D053487:DEAD-box RNA Helicases / Q000235:genetics* / Q000502:physiology; D053595:Embryonic Stem Cells / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D043244:Ribonuclease III / Q000235:genetics* / Q000502:physiology; D013234:Stem Cells
D035683:MicroRNAs; C408087:DICER1 protein, human; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases