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山中因子 - 版本历史
2026-04-18T04:36:55Z
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2025年12月29日 (一) 06:35 77921020
2025-12-29T06:35:48Z
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<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">←上一版本</td>
<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">2025年12月29日 (一) 06:35的版本</td>
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<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <p style="font-size: 1.1em; margin: 0 0 25px 0; color: #334155; text-align: justify;"></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <p style="font-size: 1.1em; margin: 0 0 25px 0; color: #334155; text-align: justify;"></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> <strong>山中因子</strong>（Yamanaka Factors）是指由日本科学家<strong>[[山中伸弥]]</strong>团队在 2006 年筛选出的四个核心<strong>[[转录因子]]</strong>：<strong>Oct3/4</strong>、<strong>Sox2</strong>、<strong>Klf4</strong> 和 <strong>c-Myc</strong>（简称 <strong>OSKM</strong>）。这组因子被誉为开启细胞“时光机”的钥匙，只需将它们导入高度分化的体细胞（如皮肤成纤维细胞）中，即可重置细胞的表观遗传状态，使其逆转为具备全能分化潜力的<strong>[[诱导多能干细胞]]</strong>（iPSC）。这一发现彻底改写了“细胞分化不可逆”的生物学定论。</div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> <strong>山中因子</strong>（Yamanaka Factors）是指由日本科学家<strong>[[山中伸弥]]</strong>团队在 2006 年筛选出的四个核心<strong>[[转录因子]]</strong>：<strong><ins class="diffchange diffchange-inline">[[</ins>Oct3/4<ins class="diffchange diffchange-inline">]]</ins></strong>、<strong><ins class="diffchange diffchange-inline">[[</ins>Sox2<ins class="diffchange diffchange-inline">]]</ins></strong>、<strong><ins class="diffchange diffchange-inline">[[</ins>Klf4<ins class="diffchange diffchange-inline">]]</ins></strong> 和 <strong><ins class="diffchange diffchange-inline">[[</ins>c-Myc<ins class="diffchange diffchange-inline">]]</ins></strong>（简称 <strong>OSKM</strong>）。这组因子被誉为开启细胞“时光机”的钥匙，只需将它们导入高度分化的体细胞（如皮肤成纤维细胞）中，即可重置细胞的表观遗传状态，使其逆转为具备全能分化潜力的<strong>[[诱导多能干细胞]]</strong>（iPSC）。这一发现彻底改写了“细胞分化不可逆”的生物学定论。</div></td></tr>
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<tr><td colspan="2" class="diff-lineno" id="mw-diff-left-l34" >第34行：</td>
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<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <th style="text-align: left; padding: 10px 15px; color: #475569; background-color: #f8fafc;">替代方案</th></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <th style="text-align: left; padding: 10px 15px; color: #475569; background-color: #f8fafc;">替代方案</th></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> <td style="padding: 10px 15px; color: #1e40af; font-weight: 600;">L-Myc, Lin28, Nanog</td></div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> <td style="padding: 10px 15px; color: #1e40af; font-weight: 600;"><ins class="diffchange diffchange-inline">[[</ins>L-Myc<ins class="diffchange diffchange-inline">]]</ins>, <ins class="diffchange diffchange-inline">[[</ins>Lin28<ins class="diffchange diffchange-inline">]]</ins>, <ins class="diffchange diffchange-inline">[[</ins>Nanog<ins class="diffchange diffchange-inline">]]</ins></td></div></td></tr>
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<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </table></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </table></div></td></tr>
<tr><td colspan="2" class="diff-lineno" id="mw-diff-left-l52" >第52行：</td>
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<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </tr></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </tr></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <tr style="border-bottom: 1px solid #e2e8f0;"></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <tr style="border-bottom: 1px solid #e2e8f0;"></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> <td style="padding: 16px 0; vertical-align: top; color: #1e40af; font-weight: bold;">Oct3/4<br><span style="font-size:0.85em; font-weight:normal; color:#64748b;">(POU5F1)</span></td></div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> <td style="padding: 16px 0; vertical-align: top; color: #1e40af; font-weight: bold;"><ins class="diffchange diffchange-inline">[[</ins>Oct3/4<ins class="diffchange diffchange-inline">]]</ins><br><span style="font-size:0.85em; font-weight:normal; color:#64748b;">(POU5F1)</span></td></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <td style="padding: 16px 0; vertical-align: top; color: #334155;"></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <td style="padding: 16px 0; vertical-align: top; color: #334155;"></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <div style="margin-bottom: 6px;"><strong>• 多能性守门人：</strong>是维持胚胎干细胞多能性的最核心因子。</div></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <div style="margin-bottom: 6px;"><strong>• 多能性守门人：</strong>是维持胚胎干细胞多能性的最核心因子。</div></div></td></tr>
<tr><td colspan="2" class="diff-lineno" id="mw-diff-left-l59" >第59行：</td>
<td colspan="2" class="diff-lineno">第59行：</td></tr>
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<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <tr style="border-bottom: 1px solid #e2e8f0;"></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <tr style="border-bottom: 1px solid #e2e8f0;"></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> <td style="padding: 16px 0; vertical-align: top; color: #1e40af; font-weight: bold;">Sox2</td></div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> <td style="padding: 16px 0; vertical-align: top; color: #1e40af; font-weight: bold;"><ins class="diffchange diffchange-inline">[[</ins>Sox2<ins class="diffchange diffchange-inline">]]</ins></td></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <td style="padding: 16px 0; vertical-align: top; color: #334155;"></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <td style="padding: 16px 0; vertical-align: top; color: #334155;"></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <div style="margin-bottom: 6px;"><strong>• 核心搭档：</strong>Oct3/4 的最佳拍档。</div></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <div style="margin-bottom: 6px;"><strong>• 核心搭档：</strong>Oct3/4 的最佳拍档。</div></div></td></tr>
<tr><td colspan="2" class="diff-lineno" id="mw-diff-left-l66" >第66行：</td>
<td colspan="2" class="diff-lineno">第66行：</td></tr>
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<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <tr style="border-bottom: 1px solid #e2e8f0;"></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <tr style="border-bottom: 1px solid #e2e8f0;"></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> <td style="padding: 16px 0; vertical-align: top; color: #1e40af; font-weight: bold;">Klf4</td></div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> <td style="padding: 16px 0; vertical-align: top; color: #1e40af; font-weight: bold;"><ins class="diffchange diffchange-inline">[[</ins>Klf4<ins class="diffchange diffchange-inline">]]</ins></td></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <td style="padding: 16px 0; vertical-align: top; color: #334155;"></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <td style="padding: 16px 0; vertical-align: top; color: #334155;"></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <div style="margin-bottom: 6px;"><strong>• 刹车松开者：</strong>抑制细胞凋亡，抑制 p53 通路。</div></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <div style="margin-bottom: 6px;"><strong>• 刹车松开者：</strong>抑制细胞凋亡，抑制 p53 通路。</div></div></td></tr>
<tr><td colspan="2" class="diff-lineno" id="mw-diff-left-l73" >第73行：</td>
<td colspan="2" class="diff-lineno">第73行：</td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </tr></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </tr></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <tr style="border-bottom: 1px solid #e2e8f0;"></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <tr style="border-bottom: 1px solid #e2e8f0;"></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> <td style="padding: 16px 0; vertical-align: top; color: #1e40af; font-weight: bold;">c-Myc</td></div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> <td style="padding: 16px 0; vertical-align: top; color: #1e40af; font-weight: bold;"><ins class="diffchange diffchange-inline">[[</ins>c-Myc<ins class="diffchange diffchange-inline">]]</ins></td></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <td style="padding: 16px 0; vertical-align: top; color: #334155;"></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <td style="padding: 16px 0; vertical-align: top; color: #334155;"></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <div style="margin-bottom: 6px;"><strong>• 增殖加速器：</strong>强效的致癌基因。</div></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <div style="margin-bottom: 6px;"><strong>• 增殖加速器：</strong>强效的致癌基因。</div></div></td></tr>
<tr><td colspan="2" class="diff-lineno" id="mw-diff-left-l84" >第84行：</td>
<td colspan="2" class="diff-lineno">第84行：</td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <div style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">从“高效”到“安全”：因子的迭代</div></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <div style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">从“高效”到“安全”：因子的迭代</div></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <p style="margin: 15px 0; text-align: justify;"></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <p style="margin: 15px 0; text-align: justify;"></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> 第一代山中因子最大的隐患在于 <strong>c-Myc</strong>。由于 c-Myc 是许多癌症（如白血病、神经母细胞瘤）的驱动基因，使用它制备的 iPS 细胞在植入体内后有形成肿瘤的风险。为了解决这一问题，科学家们进行了多轮迭代：</div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> 第一代山中因子最大的隐患在于 <strong><ins class="diffchange diffchange-inline">[[</ins>c-Myc<ins class="diffchange diffchange-inline">]]</ins></strong>。由于 c-Myc 是许多癌症（如白血病、神经母细胞瘤）的驱动基因，使用它制备的 iPS 细胞在植入体内后有形成肿瘤的风险。为了解决这一问题，科学家们进行了多轮迭代：</div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </p></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </p></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td></tr>
<tr><td colspan="2" class="diff-lineno" id="mw-diff-left-l98" >第98行：</td>
<td colspan="2" class="diff-lineno">第98行：</td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <li style="margin-bottom: 12px;"></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <li style="margin-bottom: 12px;"></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <strong>汤姆森因子 (Thomson Factors)：</strong> </div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <strong>汤姆森因子 (Thomson Factors)：</strong> </div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> 美国科学家 James Thomson 提出了另一组配方：<strong>Oct4, Sox2, Nanog, Lin28</strong>。这组因子完全不含 c-Myc，被认为在某些场景下更安全。</div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> 美国科学家 James Thomson 提出了另一组配方：<strong><ins class="diffchange diffchange-inline">[[</ins>Oct4<ins class="diffchange diffchange-inline">]]</strong></ins>, <ins class="diffchange diffchange-inline"><strong>[[</ins>Sox2<ins class="diffchange diffchange-inline">]]</strong></ins>, <ins class="diffchange diffchange-inline"><strong>[[</ins>Nanog<ins class="diffchange diffchange-inline">]]</strong></ins>, <ins class="diffchange diffchange-inline"><strong>[[</ins>Lin28<ins class="diffchange diffchange-inline">]]</ins></strong>。这组因子完全不含 c-Myc，被认为在某些场景下更安全。</div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </li></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </li></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </ul></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </ul></div></td></tr>
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77921020
https://www.yiliao.com/index.php?title=%E5%B1%B1%E4%B8%AD%E5%9B%A0%E5%AD%90&diff=311396&oldid=prev
77921020：建立内容为“<div style="padding: 0 4%; line-height: 1.8; color: #1e293b; font-family: 'Helvetica Neue', Helvetica, 'PingFang SC', Arial, sans-serif; background-color: #ffffff…”的新页面
2025-12-29T04:10:49Z
<p>建立内容为“<div style="padding: 0 4%; line-height: 1.8; color: #1e293b; font-family: 'Helvetica Neue', Helvetica, 'PingFang SC', Arial, sans-serif; background-color: #ffffff…”的新页面</p>
<p><b>新页面</b></p><div><div style="padding: 0 4%; line-height: 1.8; color: #1e293b; font-family: 'Helvetica Neue', Helvetica, 'PingFang SC', Arial, sans-serif; background-color: #ffffff; max-width: 1200px; margin: auto;"><br />
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<strong>山中因子</strong>（Yamanaka Factors）是指由日本科学家<strong>[[山中伸弥]]</strong>团队在 2006 年筛选出的四个核心<strong>[[转录因子]]</strong>：<strong>Oct3/4</strong>、<strong>Sox2</strong>、<strong>Klf4</strong> 和 <strong>c-Myc</strong>（简称 <strong>OSKM</strong>）。这组因子被誉为开启细胞“时光机”的钥匙，只需将它们导入高度分化的体细胞（如皮肤成纤维细胞）中，即可重置细胞的表观遗传状态，使其逆转为具备全能分化潜力的<strong>[[诱导多能干细胞]]</strong>（iPSC）。这一发现彻底改写了“细胞分化不可逆”的生物学定论。<br />
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<div style="font-size: 1.1em; font-weight: bold; letter-spacing: 1.2px; text-decoration: none;">山中因子 · OSKM</div><br />
<div style="font-size: 0.7em; opacity: 0.85; margin-top: 3px; white-space: nowrap;">Reprogramming Cocktail (点击展开)</div><br />
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核心公式：体细胞 + OSKM ➔ iPSC<br />
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<th style="text-align: left; padding: 10px 15px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc; width: 40%;">发现年份</th><br />
<td style="padding: 10px 15px; border-bottom: 1px solid #f1f5f9; color: #0f172a;">2006 (小鼠), 2007 (人)</td><br />
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<th style="text-align: left; padding: 10px 15px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc;">原始载体</th><br />
<td style="padding: 10px 15px; border-bottom: 1px solid #f1f5f9; color: #0f172a;">逆转录病毒 (Retrovirus)</td><br />
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<th style="text-align: left; padding: 10px 15px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc;">关键风险</th><br />
<td style="padding: 10px 15px; border-bottom: 1px solid #f1f5f9; color: #0f172a;"><strong>[[c-Myc]]</strong> 的致瘤性</td><br />
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<th style="text-align: left; padding: 10px 15px; color: #475569; background-color: #f8fafc;">替代方案</th><br />
<td style="padding: 10px 15px; color: #1e40af; font-weight: 600;">L-Myc, Lin28, Nanog</td><br />
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<div style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">四大金刚：分工与协作</div><br />
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山中因子的筛选过程最初是从 24 个候选基因开始的，最终确定的这四个因子在重编程过程中扮演着截然不同却又互补的角色，缺一不可（在早期版本中）：<br />
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<th style="padding: 12px 0; text-align: left; color: #475569; width: 22%; font-weight: bold;">因子名称</th><br />
<th style="padding: 12px 0; text-align: left; color: #475569; font-weight: bold;">功能角色与机制</th><br />
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<td style="padding: 16px 0; vertical-align: top; color: #1e40af; font-weight: bold;">Oct3/4<br><span style="font-size:0.85em; font-weight:normal; color:#64748b;">(POU5F1)</span></td><br />
<td style="padding: 16px 0; vertical-align: top; color: #334155;"><br />
<div style="margin-bottom: 6px;"><strong>• 多能性守门人：</strong>是维持胚胎干细胞多能性的最核心因子。</div><br />
<div><strong>• 作用：</strong>如果没有它，细胞无法维持未分化状态。它与其他因子形成异二聚体，启动多能性基因网络。</div><br />
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<td style="padding: 16px 0; vertical-align: top; color: #1e40af; font-weight: bold;">Sox2</td><br />
<td style="padding: 16px 0; vertical-align: top; color: #334155;"><br />
<div style="margin-bottom: 6px;"><strong>• 核心搭档：</strong>Oct3/4 的最佳拍档。</div><br />
<div><strong>• 作用：</strong>两者形成 Oct4-Sox2 复合物，结合在数千个靶基因的启动子上，既激活多能性基因，又抑制分化基因。</div><br />
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<td style="padding: 16px 0; vertical-align: top; color: #1e40af; font-weight: bold;">Klf4</td><br />
<td style="padding: 16px 0; vertical-align: top; color: #334155;"><br />
<div style="margin-bottom: 6px;"><strong>• 刹车松开者：</strong>抑制细胞凋亡，抑制 p53 通路。</div><br />
<div><strong>• 作用：</strong>作为连接核心多能性网络（Oct4/Sox2）与细胞增殖机器（c-Myc）的桥梁，平衡细胞的生与死。</div><br />
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<td style="padding: 16px 0; vertical-align: top; color: #1e40af; font-weight: bold;">c-Myc</td><br />
<td style="padding: 16px 0; vertical-align: top; color: #334155;"><br />
<div style="margin-bottom: 6px;"><strong>• 增殖加速器：</strong>强效的致癌基因。</div><br />
<div><strong>• 作用：</strong>打开染色质结构（Chromatin remodeling），让其他三个因子更容易结合到 DNA 上。虽然能显著提高重编程效率，但会大幅增加<strong>[[致瘤性]]</strong>风险。</div><br />
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<br />
<div style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">从“高效”到“安全”：因子的迭代</div><br />
<p style="margin: 15px 0; text-align: justify;"><br />
第一代山中因子最大的隐患在于 <strong>c-Myc</strong>。由于 c-Myc 是许多癌症（如白血病、神经母细胞瘤）的驱动基因，使用它制备的 iPS 细胞在植入体内后有形成肿瘤的风险。为了解决这一问题，科学家们进行了多轮迭代：<br />
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<ul style="padding-left: 25px; color: #334155;"><br />
<li style="margin-bottom: 12px;"><br />
<strong>去除 c-Myc (OSK 方案)：</strong> <br />
仅使用 Oct4, Sox2, Klf4 三个因子也能产生 iPS 细胞，虽然耗时更长、效率极低，但显著降低了致癌风险。<br />
</li><br />
<li style="margin-bottom: 12px;"><br />
<strong>L-Myc 替代：</strong> <br />
山中团队后续发现，使用 <strong>[[L-Myc]]</strong> 代替 c-Myc，既保留了促进重编程的高效率，又几乎消除了致瘤性。这是目前临床级 iPS 细胞制备的主流方案之一。<br />
</li><br />
<li style="margin-bottom: 12px;"><br />
<strong>汤姆森因子 (Thomson Factors)：</strong> <br />
美国科学家 James Thomson 提出了另一组配方：<strong>Oct4, Sox2, Nanog, Lin28</strong>。这组因子完全不含 c-Myc，被认为在某些场景下更安全。<br />
</li><br />
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<span style="color: #0f172a; font-weight: bold; font-size: 1.05em; display: inline-block; margin-bottom: 5px;">关键文献</span><br />
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[1] <strong>Takahashi K, Yamanaka S. (2006).</strong> <em>Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.</em> <strong>Cell</strong>. <br><br />
<span style="color: #475569;">[学术点评]：里程碑文献。首次向世界展示了这四个神奇的因子，开启了 iPS 时代。</span><br />
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[2] <strong>Nakagawa M, Yamanaka S, et al. (2008).</strong> <em>Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts.</em> <strong>Nature Biotechnology</strong>. <br><br />
<span style="color: #475569;">[学术点评]：报道了去除 c-Myc 的重编程方案，虽然效率下降，但证明了 c-Myc 并非绝对必要，为提高安全性指明了方向。</span><br />
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<div style="background-color: #0f172a; color: #ffffff; text-align: center; font-weight: bold; padding: 10px; letter-spacing: 1px;">山中因子 · 知识图谱关联</div><br />
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[[诱导多能干细胞]] • [[山中伸弥]] • [[转录因子]] • [[c-Myc]] • [[表观遗传学]] • [[再生医学]]<br />
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