TY - JOUR
T1 - Identification of transcription factors for lineage-specific ESC differentiation
AU - Yamamizu, Kohei
AU - Piao, Yulan
AU - Sharov, Alexei A.
AU - Zsiros, Veronika
AU - Yu, Hong
AU - Nakazawa, Kazu
AU - Schlessinger, David
AU - Ko, Minoru S.H.
N1 - Funding Information:
This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. This research was also supported in part by the Japan Science and Technology Agency, CREST program. K.Y. was supported by the postdoctoral fellowships from the Kanae Foundation, Japan, Uehara Memorial Foundation, Japan, Naito Foundation, Japan, and the Japan Society for Promotion of Science.
PY - 2013/12/17
Y1 - 2013/12/17
N2 - A network of transcription factors (TFs) determines cell identity, but identity can be altered by overexpressing a combination of TFs. However, choosing and verifying combinations of TFs for specific cell differentiation have been daunting due to the large number of possible combinations of ∼2,000 TFs. Here, we report the identification of individual TFs for lineage-specific cell differentiation based on the correlation matrix of global gene expression profiles. The overexpression of identified TFs - Myod1, Mef2c, Esx1, Foxa1, Hnf4a, Gata2, Gata3, Myc, Elf5, Irf2, Elf1, Sfpi1, Ets1, Smad7, Nr2f1, Sox11, Dmrt1, Sox9, Foxg1, Sox2, or Ascl1 - can direct efficient, specific, and rapid differentiation into myocytes, hepatocytes, blood cells, and neurons. Furthermore, transfection of synthetic mRNAs of TFs generates their appropriate target cells. These results demonstrate both the utility of this approach to identify potent TFs for cell differentiation, and the unanticipated capacity of single TFs directly guides differentiation to specific lineage fates.
AB - A network of transcription factors (TFs) determines cell identity, but identity can be altered by overexpressing a combination of TFs. However, choosing and verifying combinations of TFs for specific cell differentiation have been daunting due to the large number of possible combinations of ∼2,000 TFs. Here, we report the identification of individual TFs for lineage-specific cell differentiation based on the correlation matrix of global gene expression profiles. The overexpression of identified TFs - Myod1, Mef2c, Esx1, Foxa1, Hnf4a, Gata2, Gata3, Myc, Elf5, Irf2, Elf1, Sfpi1, Ets1, Smad7, Nr2f1, Sox11, Dmrt1, Sox9, Foxg1, Sox2, or Ascl1 - can direct efficient, specific, and rapid differentiation into myocytes, hepatocytes, blood cells, and neurons. Furthermore, transfection of synthetic mRNAs of TFs generates their appropriate target cells. These results demonstrate both the utility of this approach to identify potent TFs for cell differentiation, and the unanticipated capacity of single TFs directly guides differentiation to specific lineage fates.
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U2 - 10.1016/j.stemcr.2013.10.006
DO - 10.1016/j.stemcr.2013.10.006
M3 - Article
C2 - 24371809
AN - SCOPUS:84890899156
SN - 2213-6711
VL - 1
SP - 545
EP - 559
JO - Stem cell reports
JF - Stem cell reports
IS - 6
ER -