Abstract
Summary Sox2 is a key player in the maintenance of pluripotency and stemness, and thus inhibition of its function would abrogate the stemness of pluripotent cells and induce differentiation into several types of cells. Herein we describe a strategy that relies on a combination of Sox2 inhibition with lineage-specific induction to promote efficient and selective differentiation of pluripotent P19 cells into neurons. When P19 cells transduced with Skp protein, an inhibitor of Sox2, are incubated with a neurogenesis inducer, the cells are selectively converted into neurons that generate depolarization-induced sodium currents and action potentials. This finding indicates that the differentiated neurons are electrophysiologically active. Signaling pathway studies lead us to conclude that a combination of Skp with the neurogenesis inducer enhances neurogenesis in P19 cells by activating Wnt and Notch pathways. The present differentiation protocol could be valuable to selectively generate functionally active neurons from pluripotent cells.
| Original language | English |
|---|---|
| Pages (from-to) | 1512-1520 |
| Number of pages | 9 |
| Journal | Chemistry and Biology |
| Volume | 22 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - 2015 Nov 19 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmacology
- Drug Discovery
- Clinical Biochemistry
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Combining Suppression of Stemness with Lineage-Specific Induction Leads to Conversion of Pluripotent Cells into Functional Neurons. / Halder, Debasish; Chang, Gyeong Eon; De, Debojyoti; Cheong, Eunji; Kim, Kyeong Kyu; Shin, Injae.
In: Chemistry and Biology, Vol. 22, No. 11, 19.11.2015, p. 1512-1520.Research output: Contribution to journal › Article
TY - JOUR
T1 - Combining Suppression of Stemness with Lineage-Specific Induction Leads to Conversion of Pluripotent Cells into Functional Neurons
AU - Halder, Debasish
AU - Chang, Gyeong Eon
AU - De, Debojyoti
AU - Cheong, Eunji
AU - Kim, Kyeong Kyu
AU - Shin, Injae
PY - 2015/11/19
Y1 - 2015/11/19
N2 - Summary Sox2 is a key player in the maintenance of pluripotency and stemness, and thus inhibition of its function would abrogate the stemness of pluripotent cells and induce differentiation into several types of cells. Herein we describe a strategy that relies on a combination of Sox2 inhibition with lineage-specific induction to promote efficient and selective differentiation of pluripotent P19 cells into neurons. When P19 cells transduced with Skp protein, an inhibitor of Sox2, are incubated with a neurogenesis inducer, the cells are selectively converted into neurons that generate depolarization-induced sodium currents and action potentials. This finding indicates that the differentiated neurons are electrophysiologically active. Signaling pathway studies lead us to conclude that a combination of Skp with the neurogenesis inducer enhances neurogenesis in P19 cells by activating Wnt and Notch pathways. The present differentiation protocol could be valuable to selectively generate functionally active neurons from pluripotent cells.
AB - Summary Sox2 is a key player in the maintenance of pluripotency and stemness, and thus inhibition of its function would abrogate the stemness of pluripotent cells and induce differentiation into several types of cells. Herein we describe a strategy that relies on a combination of Sox2 inhibition with lineage-specific induction to promote efficient and selective differentiation of pluripotent P19 cells into neurons. When P19 cells transduced with Skp protein, an inhibitor of Sox2, are incubated with a neurogenesis inducer, the cells are selectively converted into neurons that generate depolarization-induced sodium currents and action potentials. This finding indicates that the differentiated neurons are electrophysiologically active. Signaling pathway studies lead us to conclude that a combination of Skp with the neurogenesis inducer enhances neurogenesis in P19 cells by activating Wnt and Notch pathways. The present differentiation protocol could be valuable to selectively generate functionally active neurons from pluripotent cells.
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UR - http://www.scopus.com/inward/citedby.url?scp=84947746334&partnerID=8YFLogxK
U2 - 10.1016/j.chembiol.2015.10.008
DO - 10.1016/j.chembiol.2015.10.008
M3 - Article
C2 - 26590637
AN - SCOPUS:84947746334
VL - 22
SP - 1512
EP - 1520
JO - Cell Chemical Biology
JF - Cell Chemical Biology
SN - 2451-9448
IS - 11
ER -