Cell type determination for cardiac differentiation occurs soon after seeding of human-induced pluripotent stem cells.
Cell type determination for cardiac differentiation occurs soon after seeding of human-induced pluripotent stem cells.
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在接种人诱导多能干细胞后不久就会进行心脏分化的细胞类型测定。
DOI：
10.1186/s13059-022-02654-6
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发表时间：
2022-04-05
期刊：
影响因子：
12.3
通讯作者：
Raj A
中科院分区：
文献类型：
--
作者：
Jiang CL;Goyal Y;Jain N;Wang Q;Truitt RE;Coté AJ;Emert B;Mellis IA;Kiani K;Yang W;Jain R;Raj A
人类诱导多能干细胞(HIPS)的心脏分化持续产生心肌细胞和非心脏细胞类型的混合群体，即使使用特征良好的方案也是如此。我们试图确定不同的细胞类型是否可能是HIPS细胞在分化开始之前的内在差异所致。通过关联共享相同HIPS细胞前体的单个分化细胞，我们测试了HIPS细胞状态是否预先决定了表达的可变性。在一项单独的实验中，与分化群体中的其他细胞相比，共享同一祖细胞的细胞彼此在转录上更相似。然而，当相同的髋关节细胞平行分化时，我们没有观察到跨分化的高转录相似性。此外，我们发现在分化过程中会发生大量的细胞死亡，这表明所有细胞存活或死亡的可能性都是一样的，这表明特定HIPS细胞前体细胞的后代没有内在的选择偏见。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，所以我们通过标记基因的表达来标记细胞，发现表达相同标记的细胞往往出现在斑块中。我们的结果表明，一旦启动了跨多种细胞类型的细胞类型确定，就会在多个分裂中以细胞自主的方式保持。总之，我们的结果表明，尽管在最初的HIPS细胞群体中存在显著的异质性，但它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在HIPS细胞播种分化后不久开始发挥作用。网上版载有补充材料，可在10.1186/s13059-022-02654-6查阅。
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. 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. 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. The online version contains supplementary material available at 10.1186/s13059-022-02654-6.
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影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
外周血单核细胞衍生的多能干细胞的高度纯化的人类心肌细胞产生。
影响因子：
3.7
作者：
Fuerstenau-Sharp M;Zimmermann ME;Stark K;Jentsch N;Klingenstein M;Drzymalski M;Wagner S;Maier LS;Hehr U;Baessler A;Fischer M;Hengstenberg C
通讯作者：
Hengstenberg C
影响因子：
64.8
作者：
Arumugam, Manimozhiyan;Raes, Jeroen;Pelletier, Eric;Le Paslier, Denis;Yamada, Takuji;Mende, Daniel R.;Fernandes, Gabriel R.;Tap, Julien;Bruls, Thomas;Batto, Jean-Michel;Bertalan, Marcelo;Borruel, Natalia;Casellas, Francesc;Fernandez, Leyden;Gautier, Laurent;Hansen, Torben;Hattori, Masahira;Hayashi, Tetsuya;Kleerebezem, Michiel;Kurokawa, Ken;Leclerc, Marion;Levenez, Florence;Manichanh, Chaysavanh;Nielsen, H. Bjorn;Nielsen, Trine;Pons, Nicolas;Poulain, Julie;Qin, Junjie;Sicheritz-Ponten, Thomas;Tims, Sebastian;Torrents, David;Ugarte, Edgardo;Zoetendal, Erwin G.;Wang, Jun;Guarner, Francisco;Pedersen, Oluf;de Vos, Willem M.;Brunak, Soren;Dore, Joel;Weissenbach, Jean;Ehrlich, S. Dusko;Bork, Peer
通讯作者：
Bork, Peer
影响因子：
5.9
作者：
Allison TF;Smith AJH;Anastassiadis K;Sloane-Stanley J;Biga V;Stavish D;Hackland J;Sabri S;Langerman J;Jones M;Plath K;Coca D;Barbaric I;Gokhale P;Andrews PW
通讯作者：
Andrews PW
影响因子：
10.5
作者：
Cabili, Moran N.;Trapnell, Cole;Rinn, John L.
通讯作者：
Rinn, John L.