Cyclin D Genes Enhance iPS Cell Reprogramming

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Solution Overview

Problem

The efficiency of establishing induced pluripotent stem cells (iPS cells) is low, particularly when using three factors (Oct3/4, Sox2, and Klf4) without c-Myc, which can lead to tumorigenesis, and the mechanisms involving the p53-p21 pathway in reprogramming somatic cells remain unclear.

Innovation Solution

Introducing genes from the cyclin D family, such as cyclin D1, D2, and D3, into somatic cells during nuclear reprogramming to enhance iPS cell establishment efficiency, alongside established nuclear reprogramming factors like Oct3/4, Sox2, and Klf4, to improve the reprogramming process without inhibiting the p53 pathway.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If c-Myc gene is used in nuclear reprogramming, then iPS cell establishment efficiency is improved, but tumorigenesis risk increases

Engineering Contradiction:

ImproveiPS cell establishment efficiencyVSAvoidtumorigenesis risk

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The invention extracts and removes the harmful c-Myc gene from the nuclear reprogramming factor combination while maintaining efficient iPS cell establishment through alternative factors (c-Myc negative combination), thereby eliminating tumorigenesis risk while preserving productivity

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The invention changes the parameter composition of nuclear reprogramming factors by substituting c-Myc with alternative transcription factors or combinations, achieving the same functional outcome (high efficiency) without the harmful effects

Inventive Principle:

Principle #35Parameter changes

2Productivity

If p53 pathway is inhibited to improve reprogramming efficiency, then iPS cell establishment efficiency is improved, but genome stability control is compromised

Engineering Contradiction:

ImproveiPS cell establishment efficiencyVSAvoidgenome stability control

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The invention converts the potential harm of p53 pathway interference by using indirect approaches (enhancing DNA damage response, modulating cell cycle) rather than direct inhibition, thereby maintaining genome stability control while achieving high reprogramming efficiency

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The invention introduces intermediary mechanisms (DNA damage response enhancement, cell cycle modulation) that mediate between the need for high reprogramming efficiency and the requirement for maintaining p53-mediated genome stability control

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS9637732B2Method of efficiently establishing induced pluripotent stem cells

Publication Date: 2017.05.02 TANABE KOJI

AI summary

Provided is a method of improving the efficiency of iPS cell establishment, comprising bringing one or more factors selected from the group consisting of proteins belonging to cyclin D family and nucleic acids that encode the same into contact with a somatic cell, in the step of nuclear reprogramming of the somatic cell. Also provided are a method of producing an iPS cell comprising the step of bringing the factor(s) and nuclear reprogramming substance(s) into contact with a somatic cell, an iPS cell comprising a nucleic acid that encodes a protein belonging to cyclin D family that can be obtained by the method of producing an iPS cell, and a method of somatic cell production by forcing the iPS cell to differentiate.