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OCT4: A penetrant pluripotency inducer.

Wang X, Jauch R - Cell Regen (Lond) (2014)

Bottom Line: Native OCT4 protein has the intrinsic ability of crossing cellular membranes to enter cells.This finding could revive efforts to induce pluripotency with proteins replacing nucleic acid-based approaches, and raises the intriguing question as to whether OCT4 can act non-cell-autonomously.

View Article: PubMed Central - PubMed

Affiliation: Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences (GIBH), 190 Kai Yuan Avenue, Science Park, Guangzhou, 510530 China.

ABSTRACT
Native OCT4 protein has the intrinsic ability of crossing cellular membranes to enter cells. This finding could revive efforts to induce pluripotency with proteins replacing nucleic acid-based approaches, and raises the intriguing question as to whether OCT4 can act non-cell-autonomously.

No MeSH data available.


Related in: MedlinePlus

The third helix of the human OCT4 protein contains a cell penetrating peptide (orange) enabling the native protein to enter somatic cells. Potentially, native (or truncated) OCT4 can be used to generate integration-free piPSCs in combination with other factors such as small molecules [22] or other cell-penetrating factors and activators of the innate immunity [15] (indicated as ‘X’ in the figure) that can serve as raw materials to produce clinical grade cells for safe cell therapy.
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Fig1: The third helix of the human OCT4 protein contains a cell penetrating peptide (orange) enabling the native protein to enter somatic cells. Potentially, native (or truncated) OCT4 can be used to generate integration-free piPSCs in combination with other factors such as small molecules [22] or other cell-penetrating factors and activators of the innate immunity [15] (indicated as ‘X’ in the figure) that can serve as raw materials to produce clinical grade cells for safe cell therapy.

Mentions: The use of recombinant proteins for cellular reprogramming would eliminate the risks of nucleic acid based approaches and could prove to be a versatile way to generate iPSCs. Notably, a truncated version of the transcription factor Nanog consisting of only the 70 amino acid homedomain retains the capacity to promote reprogramming [17]. Similarly, versions of Sox proteins trimmed to their DNA binding high mobility group (HMG) domain still support reprogramming when a VP16 transactivation domain is added [18]. Collectively, one might thus envisage cocktails of reprogramming factors, truncated and/or enhanced with transactivation domains and CPPs [19], that readily cross cellular membranes and promote reprogramming (Figure 1). Previously, poor delivery, the cumbersome production of recombinant proteins and low reprogramming efficiency has hampered the widespread use of piPSCs. Yet, self-penetrating proteins (e.g. OCT4) and truncated proteins might be more readily available and unleash a renaissance of the piPSCs technology. Clearly, proteins could allow for more accurate dosing, highly defined timing of factor exposure and maximal control over the sequence of factor addition not easily possible with other techniques. Controllability is very desirable, since both the efficiency [20] as well as the outcome [21] strongly depends on exposure time and the sequence of factor addition. The recently reported production of chemically induced pluripotent stem cells (CiPSCs) that relied solely on a combination of 7 small-molecule compounds [22] is another promising alternative to standard reprogramming approaches, but still awaits widespread acceptance in the field.Figure 1


OCT4: A penetrant pluripotency inducer.

Wang X, Jauch R - Cell Regen (Lond) (2014)

The third helix of the human OCT4 protein contains a cell penetrating peptide (orange) enabling the native protein to enter somatic cells. Potentially, native (or truncated) OCT4 can be used to generate integration-free piPSCs in combination with other factors such as small molecules [22] or other cell-penetrating factors and activators of the innate immunity [15] (indicated as ‘X’ in the figure) that can serve as raw materials to produce clinical grade cells for safe cell therapy.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4230516&req=5

Fig1: The third helix of the human OCT4 protein contains a cell penetrating peptide (orange) enabling the native protein to enter somatic cells. Potentially, native (or truncated) OCT4 can be used to generate integration-free piPSCs in combination with other factors such as small molecules [22] or other cell-penetrating factors and activators of the innate immunity [15] (indicated as ‘X’ in the figure) that can serve as raw materials to produce clinical grade cells for safe cell therapy.
Mentions: The use of recombinant proteins for cellular reprogramming would eliminate the risks of nucleic acid based approaches and could prove to be a versatile way to generate iPSCs. Notably, a truncated version of the transcription factor Nanog consisting of only the 70 amino acid homedomain retains the capacity to promote reprogramming [17]. Similarly, versions of Sox proteins trimmed to their DNA binding high mobility group (HMG) domain still support reprogramming when a VP16 transactivation domain is added [18]. Collectively, one might thus envisage cocktails of reprogramming factors, truncated and/or enhanced with transactivation domains and CPPs [19], that readily cross cellular membranes and promote reprogramming (Figure 1). Previously, poor delivery, the cumbersome production of recombinant proteins and low reprogramming efficiency has hampered the widespread use of piPSCs. Yet, self-penetrating proteins (e.g. OCT4) and truncated proteins might be more readily available and unleash a renaissance of the piPSCs technology. Clearly, proteins could allow for more accurate dosing, highly defined timing of factor exposure and maximal control over the sequence of factor addition not easily possible with other techniques. Controllability is very desirable, since both the efficiency [20] as well as the outcome [21] strongly depends on exposure time and the sequence of factor addition. The recently reported production of chemically induced pluripotent stem cells (CiPSCs) that relied solely on a combination of 7 small-molecule compounds [22] is another promising alternative to standard reprogramming approaches, but still awaits widespread acceptance in the field.Figure 1

Bottom Line: Native OCT4 protein has the intrinsic ability of crossing cellular membranes to enter cells.This finding could revive efforts to induce pluripotency with proteins replacing nucleic acid-based approaches, and raises the intriguing question as to whether OCT4 can act non-cell-autonomously.

View Article: PubMed Central - PubMed

Affiliation: Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences (GIBH), 190 Kai Yuan Avenue, Science Park, Guangzhou, 510530 China.

ABSTRACT
Native OCT4 protein has the intrinsic ability of crossing cellular membranes to enter cells. This finding could revive efforts to induce pluripotency with proteins replacing nucleic acid-based approaches, and raises the intriguing question as to whether OCT4 can act non-cell-autonomously.

No MeSH data available.


Related in: MedlinePlus