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利用 ACAN-2A-mScarlet 报告基因人 iPSC 系分离和追踪基质产生的脊索细胞和软骨细胞。

Isolation and tracing of matrix-producing notochordal and chondrocyte cells using ACAN-2A-mScarlet reporter human iPSC lines.

机构信息

Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 108, 3584 CM Utrecht, Netherlands.

Department of Biomedical Data Sciences, Section Molecular Epidemiology, Leiden University Medical Center, Leiden, Netherlands.

出版信息

Sci Adv. 2024 Oct 25;10(43):eadp3170. doi: 10.1126/sciadv.adp3170. Epub 2024 Oct 23.

DOI:10.1126/sciadv.adp3170
PMID:39441923
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11498221/
Abstract

The development of human induced pluripotent stem cell (iPSC)-based regenerative therapies is challenged by the lack of specific cell markers to isolate differentiated cell types and improve differentiation protocols. This issue is particularly critical for notochordal-like cells and chondrocytes, which are crucial in treating back pain and osteoarthritis, respectively. Both cell types produce abundant proteoglycan aggrecan (ACAN), crucial for the extracellular matrix. We generated two human iPSC lines containing an ACAN-2A-mScarlet reporter. The reporter cell lines were validated using CRISPR-mediated transactivation and functionally validated during notochord and cartilage differentiation. The ability to isolate differentiated cell populations producing ACAN enables their enrichment even in the absence of specific cell markers and allows for comprehensive studies and protocol refinement. ACAN's prevalence in various tissues (e.g., cardiac and cerebral) underscores the reporter's versatility as a valuable tool for tracking matrix protein production in diverse cell types, benefiting developmental biology, matrix pathophysiology, and regenerative medicine.

摘要

基于人诱导多能干细胞（iPSC）的再生治疗的发展受到缺乏特定细胞标记物来分离分化细胞类型和改进分化方案的限制。对于类脊索细胞和软骨细胞来说，这个问题尤其关键，因为它们分别在治疗背痛和骨关节炎方面起着至关重要的作用。这两种细胞类型都产生丰富的蛋白聚糖聚集蛋白聚糖（ACAN），这对于细胞外基质至关重要。我们生成了两条含有 ACAN-2A-mScarlet 报告基因的人 iPSC 系。使用 CRISPR 介导的转激活验证了报告细胞系，并在脊索和软骨分化过程中对其功能进行了验证。分离产生 ACAN 的分化细胞群体的能力使得即使在缺乏特定细胞标记物的情况下也能够对其进行富集，并且允许进行全面的研究和方案优化。ACAN 在各种组织（例如心脏和大脑）中的普遍存在突出了该报告基因作为跟踪不同细胞类型中基质蛋白产生的有价值工具的多功能性，这有益于发育生物学、基质病理生理学和再生医学。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9661/11498221/296e988c7743/sciadv.adp3170-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9661/11498221/5e3207d13053/sciadv.adp3170-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9661/11498221/88b4e338a52e/sciadv.adp3170-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9661/11498221/1cc139710cfc/sciadv.adp3170-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9661/11498221/d0939276a507/sciadv.adp3170-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9661/11498221/fa1f2f75daa2/sciadv.adp3170-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9661/11498221/296e988c7743/sciadv.adp3170-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9661/11498221/5e3207d13053/sciadv.adp3170-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9661/11498221/88b4e338a52e/sciadv.adp3170-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9661/11498221/1cc139710cfc/sciadv.adp3170-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9661/11498221/d0939276a507/sciadv.adp3170-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9661/11498221/fa1f2f75daa2/sciadv.adp3170-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9661/11498221/296e988c7743/sciadv.adp3170-f6.jpg

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