Cell type determination for cardiac differentiation occurs soon after seeding of human-induced pluripotent stem cells.

IF 12.3 1区 生物学 Q1 Agricultural and Biological Sciences Genome Biology Pub Date : 2022-04-05 DOI:10.1186/s13059-022-02654-6
Connie L Jiang, Yogesh Goyal, Naveen Jain, Qiaohong Wang, Rachel E Truitt, Allison J Coté, Benjamin Emert, Ian A Mellis, Karun Kiani, Wenli Yang, Rajan Jain, Arjun Raj
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Abstract

Background: Cardiac differentiation of human-induced pluripotent stem (hiPS) cells consistently produces a mixed population of cardiomyocytes and non-cardiac cell types, even when using well-characterized protocols. We sought to determine whether different cell types might result from intrinsic differences in hiPS cells prior to the onset of differentiation.

Results: By associating individual differentiated cells that share a common hiPS cell precursor, we tested whether expression variability is predetermined from the hiPS cell state. In a single experiment, cells that shared a progenitor were more transcriptionally similar to each other than to other cells in the differentiated population. However, when the same hiPS cells were differentiated in parallel, we did not observe high transcriptional similarity across differentiations. Additionally, we found that substantial cell death occurs during differentiation in a manner that suggested all cells were equally likely to survive or die, suggesting that there is no intrinsic selection bias for cells descended from particular hiPS cell progenitors. We thus wondered how cells grow spatially during differentiation, so we labeled cells by expression of marker genes and found that cells expressing the same marker tended to occur in patches. Our results suggest that cell type determination across multiple cell types, once initiated, is maintained in a cell-autonomous manner for multiple divisions.

Conclusions: Altogether, our results show that while substantial heterogeneity exists in the initial hiPS cell population, it is not responsible for the variability observed in differentiated outcomes; instead, factors specifying the various cell types likely act during a window that begins shortly after the seeding of hiPS cells for differentiation.

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人类诱导多能干细胞播种后,很快就会确定心脏分化的细胞类型。
背景:人类诱导多能干细胞(hiPS)的心脏分化始终会产生心肌细胞和非心脏细胞类型的混合群体,即使在使用特征良好的方案时也是如此。我们试图确定不同的细胞类型是否可能源于hiPS细胞在开始分化前的内在差异:通过将具有共同 hiPS 细胞前体的单个分化细胞联系起来,我们测试了表达变异性是否是由 hiPS 细胞状态预先决定的。在一次实验中,与分化群体中的其他细胞相比,共享一个祖细胞的细胞在转录上更加相似。然而,当相同的 hiPS 细胞平行分化时,我们并没有观察到不同分化细胞之间的转录相似性很高。此外,我们还发现在分化过程中会出现大量的细胞死亡,这表明所有细胞存活或死亡的可能性都是相同的,这说明对于特定的 hiPS 细胞祖细胞所产生的细胞并不存在内在的选择偏差。因此,我们想知道细胞在分化过程中是如何在空间上生长的,所以我们用标记基因的表达来标记细胞,结果发现表达相同标记基因的细胞往往成片出现。我们的结果表明,多种细胞类型的细胞类型决定一旦启动,就会以细胞自主的方式维持多次分裂:总之,我们的研究结果表明,虽然初始 hiPS 细胞群中存在大量异质性,但这并不是分化结果中观察到的变异性的原因;相反,指定各种细胞类型的因素可能是在 hiPS 细胞播种分化后不久开始作用的一个窗口期。
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来源期刊
Genome Biology
Genome Biology BIOTECHNOLOGY & APPLIED MICROBIOLOGY-GENETICS & HEREDITY
CiteScore
25.50
自引率
3.30%
发文量
0
审稿时长
14 weeks
期刊介绍: Genome Biology is a leading research journal that focuses on the study of biology and biomedicine from a genomic and post-genomic standpoint. The journal consistently publishes outstanding research across various areas within these fields. With an impressive impact factor of 12.3 (2022), Genome Biology has earned its place as the 3rd highest-ranked research journal in the Genetics and Heredity category, according to Thomson Reuters. Additionally, it is ranked 2nd among research journals in the Biotechnology and Applied Microbiology category. It is important to note that Genome Biology is the top-ranking open access journal in this category. In summary, Genome Biology sets a high standard for scientific publications in the field, showcasing cutting-edge research and earning recognition among its peers.
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