• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

维甲酸调控指导人诱导多能干细胞向左或右心室样心肌细胞分化。

Retinoic acid modulation guides human-induced pluripotent stem cell differentiation towards left or right ventricle-like cardiomyocytes.

机构信息

Walter Brendel Center for Experimental Medicine (WBex), University Clinic Munich, LMU Munich, 81377, Munich, Germany.

Center for Cardiovascular Research (DZHK), Munich Heart Alliance (MHA), Partner Site Munich, 81377, Munich, Germany.

出版信息

Stem Cell Res Ther. 2024 Jun 21;15(1):184. doi: 10.1186/s13287-024-03741-0.

DOI:10.1186/s13287-024-03741-0
PMID:38902843
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11191368/
Abstract

BACKGROUND

Cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSCs) by traditional methods are a mix of atrial and ventricular CMs and many other non-cardiomyocyte cells. Retinoic acid (RA) plays an important role in regulation of the spatiotemporal development of the embryonic heart.

METHODS

CMs were derived from hiPSC (hi-PCS-CM) using different concentrations of RA (Control without RA, LRA with 0.05μM and HRA with 0.1 μM) between day 3-6 of the differentiation process. Engineered heart tissues (EHTs) were generated by assembling hiPSC-CM at high cell density in a low collagen hydrogel.

RESULTS

In the HRA group, hiPSC-CMs exhibited highest expression of contractile proteins MYH6, MYH7 and cTnT. The expression of TBX5, NKX2.5 and CORIN, which are marker genes for left ventricular CMs, was also the highest in the HRA group. In terms of EHT, the HRA group displayed the highest contraction force, the lowest beating frequency, and the highest sensitivity to hypoxia and isoprenaline, which means it was functionally more similar to the left ventricle. RNAsequencing revealed that the heightened contractility of EHT within the HRA group can be attributed to the promotion of augmented extracellular matrix strength by RA.

CONCLUSION

By interfering with the differentiation process of hiPSC with a specific concentration of RA at a specific time, we were able to successfully induce CMs and EHTs with a phenotype similar to that of the left ventricle or right ventricle.

摘要

背景

通过传统方法从人诱导多能干细胞（hiPSC）中获得的心肌细胞（CMs）是心房和心室 CMs 以及许多其他非心肌细胞的混合物。视黄酸（RA）在胚胎心脏时空发育的调节中起着重要作用。

方法

在分化过程的第 3-6 天，使用不同浓度的 RA（无 RA 的对照、0.05μM 的 LRA 和 0.1μM 的 HRA）将 hiPSC 衍生为 CMs（hi-PCS-CM）。通过在低胶原水凝胶中以高细胞密度组装 hiPSC-CM 来生成工程心脏组织（EHT）。

结果

在 HRA 组中，hiPSC-CMs 表现出最高水平的收缩蛋白 MYH6、MYH7 和 cTnT 的表达。TBX5、NKX2.5 和 CORIN 的表达也最高，它们是左心室 CMs 的标志物基因。在 EHT 方面，HRA 组表现出最高的收缩力、最低的跳动频率以及对缺氧和异丙肾上腺素的最高敏感性，这意味着它在功能上更类似于左心室。RNA 测序表明，HRA 组内 EHT 的收缩性增强可归因于 RA 促进细胞外基质强度的增强。

结论

通过在特定时间用特定浓度的 RA 干扰 hiPSC 的分化过程，我们能够成功诱导出具有类似于左心室或右心室表型的 CMs 和 EHT。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5db5/11191368/b07eb169e05d/13287_2024_3741_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5db5/11191368/5b465e5dee88/13287_2024_3741_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5db5/11191368/72772d21e328/13287_2024_3741_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5db5/11191368/3282819cf9c4/13287_2024_3741_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5db5/11191368/ebfdbf46e310/13287_2024_3741_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5db5/11191368/f97529c72bd3/13287_2024_3741_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5db5/11191368/c97150b7d044/13287_2024_3741_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5db5/11191368/b07eb169e05d/13287_2024_3741_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5db5/11191368/5b465e5dee88/13287_2024_3741_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5db5/11191368/72772d21e328/13287_2024_3741_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5db5/11191368/3282819cf9c4/13287_2024_3741_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5db5/11191368/ebfdbf46e310/13287_2024_3741_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5db5/11191368/f97529c72bd3/13287_2024_3741_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5db5/11191368/c97150b7d044/13287_2024_3741_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5db5/11191368/b07eb169e05d/13287_2024_3741_Fig7_HTML.jpg

相似文献

1
Retinoic acid modulation guides human-induced pluripotent stem cell differentiation towards left or right ventricle-like cardiomyocytes.维甲酸调控指导人诱导多能干细胞向左或右心室样心肌细胞分化。
Stem Cell Res Ther. 2024 Jun 21;15(1):184. doi: 10.1186/s13287-024-03741-0.
2
Bioorthogonal non-canonical amino acid tagging to track transplanted human induced pluripotent stem cell-specific proteome.生物正交非天然氨基酸标记追踪移植的人诱导多能干细胞特异性蛋白质组。
Stem Cell Res Ther. 2024 Jun 26;15(1):186. doi: 10.1186/s13287-024-03792-3.
3
hiPSC-CM electrophysiology: impact of temporal changes and study parameters on experimental reproducibility.人诱导多能干细胞心肌细胞电生理学：时间变化和研究参数对实验可重复性的影响。
Am J Physiol Heart Circ Physiol. 2024 Jul 1;327(1):H12-H27. doi: 10.1152/ajpheart.00631.2023. Epub 2024 May 10.
4
Pre-clinical evaluation of the efficacy and safety of human induced pluripotent stem cell-derived cardiomyocyte patch.人诱导多能干细胞衍生心肌细胞贴片的疗效和安全性的临床前评估。
Stem Cell Res Ther. 2024 Mar 13;15(1):73. doi: 10.1186/s13287-024-03690-8.
5
Advanced tissue-engineered pulsatile conduit using human induced pluripotent stem cell-derived cardiomyocytes.使用人诱导多能干细胞衍生的心肌细胞构建的先进组织工程搏动性管道。
Acta Biomater. 2025 Jun 27. doi: 10.1016/j.actbio.2025.06.055.
6
Adipocyte-mediated electrophysiological remodeling of human stem cell - derived cardiomyocytes.脂肪细胞介导的人干细胞源性心肌细胞的电生理重构。
J Mol Cell Cardiol. 2024 Apr;189:52-65. doi: 10.1016/j.yjmcc.2024.02.002. Epub 2024 Feb 10.
7
Reduced Graphene-Oxide-Doped Elastic Biodegradable Polyurethane Fibers for Cardiomyocyte Maturation.还原氧化石墨烯掺杂弹性可生物降解聚氨酯纤维促进心肌细胞成熟。
ACS Biomater Sci Eng. 2024 Jun 10;10(6):3759-3774. doi: 10.1021/acsbiomaterials.3c01908. Epub 2024 May 27.
8
HAND factors regulate cardiac lineage commitment and differentiation from human pluripotent stem cells.HAND 因子调控人类多能干细胞向心脏谱系的定向分化。
Stem Cell Res Ther. 2024 Feb 5;15(1):31. doi: 10.1186/s13287-024-03649-9.
9
Allogenic mitochondria transfer improves cardiac function in iPS-cell-differentiated cardiomyocytes of a patient with Barth syndrome.异体线粒体转移可改善一名患有巴斯综合征患者的诱导多能干细胞分化心肌细胞的心脏功能。
Exp Mol Med. 2025 Jun 24. doi: 10.1038/s12276-025-01472-7.
10
Atrial Fibrillation Related Titin Truncation Is Associated With Atrial Myopathy in Patient-Derived Induced Pluripotent Stem Cell Disease Models.在患者来源的诱导多能干细胞疾病模型中，心房颤动相关的肌联蛋白截短与心房心肌病相关。
Circ Genom Precis Med. 2025 Feb;18(1):e004412. doi: 10.1161/CIRCGEN.123.004412. Epub 2025 Jan 24.

引用本文的文献

1
Bioengineering Approaches to In Vitro Modeling of Genetic and Acquired Cardiac Diseases.用于遗传性和后天性心脏病体外建模的生物工程方法。
Curr Cardiol Rep. 2025 Mar 20;27(1):72. doi: 10.1007/s11886-025-02218-7.

本文引用的文献

1
Retinoic acid signaling modulation guides in vitro specification of human heart field-specific progenitor pools.维甲酸信号转导调控指导人心脏场特异祖细胞库的体外特化。
Nat Commun. 2023 Apr 3;14(1):1722. doi: 10.1038/s41467-023-36764-x.
2
Excessive Trabeculation of the Left Ventricle: JACC: Cardiovascular Imaging Expert Panel Paper.左心室小梁过度增生：JACC：心血管成像专家小组论文。
JACC Cardiovasc Imaging. 2023 Mar;16(3):408-425. doi: 10.1016/j.jcmg.2022.12.026. Epub 2023 Feb 8.
3
Chemical and mechanical activation of resident cardiac macrophages in the living myocardial slice ex vivo model.
在活体心肌切片模型中，对驻留心肌巨噬细胞进行化学和机械激活。
Basic Res Cardiol. 2022 Nov 30;117(1):63. doi: 10.1007/s00395-022-00971-2.
4
The SOCE Machinery: An Unbalanced Knowledge between Left and Right Ventricular Pathophysiology.左、右心室病理生理学之间不平衡的知识：SOCE 机制。
Cells. 2022 Oct 18;11(20):3282. doi: 10.3390/cells11203282.
5
RA signaling pathway combined with Wnt signaling pathway regulates human-induced pluripotent stem cells (hiPSCs) differentiation to sinus node-like cells.RA 信号通路与 Wnt 信号通路共同调控人诱导多能干细胞（hiPSCs）向窦房结样细胞分化。
Stem Cell Res Ther. 2022 Jul 18;13(1):324. doi: 10.1186/s13287-022-03006-8.
6
Desmin deficiency affects the microenvironment of the cardiac side population and Sca1 stem cell population of the adult heart and impairs their cardiomyogenic commitment.结蛋白缺乏影响成年心脏的心脏侧群和 Sca1 干细胞群的微环境，并损害它们的心肌生成能力。
Cell Tissue Res. 2022 Aug;389(2):309-326. doi: 10.1007/s00441-022-03643-8. Epub 2022 Jun 4.
7
Post-Transcriptional Regulation of Molecular Determinants during Cardiogenesis.心脏发生过程中分子决定因素的转录后调控。
Int J Mol Sci. 2022 Mar 4;23(5):2839. doi: 10.3390/ijms23052839.
8
MEF2 in cardiac hypertrophy in response to hypertension.肌细胞增强因子 2 在高血压引起的心肌肥厚中的作用。
Trends Cardiovasc Med. 2023 May;33(4):204-212. doi: 10.1016/j.tcm.2022.01.002. Epub 2022 Jan 11.
9
Retinoic acid signaling in heart development: Application in the differentiation of cardiovascular lineages from human pluripotent stem cells.视黄酸信号在心脏发育中的作用：在人类多能干细胞向心血管谱系分化中的应用。
Stem Cell Reports. 2021 Nov 9;16(11):2589-2606. doi: 10.1016/j.stemcr.2021.09.010. Epub 2021 Oct 14.
10
Human iPS-derived pre-epicardial cells direct cardiomyocyte aggregation expansion and organization in vitro.人诱导多能干细胞衍生的原始心外膜细胞在体外指导心肌细胞的聚集、扩增和组织。
Nat Commun. 2021 Aug 17;12(1):4997. doi: 10.1038/s41467-021-24921-z.