Molecular programs initiating cell fate divergence (CFD) are difficult to identify. Current approaches usually compare cells long after CFD initiation, therefore missing molecular changes at its start. Ideally, single cells that differ in their CFD molecular program but are otherwise identical are compared early in CFD. This is possible in diverging sister cells, which were identical until their mother's division and thus differ mainly in CFD properties. In asymmetrically dividing cells, divergent daughter fates are prospectively committed during division, and diverging sisters can thus be identified at the start of CFD. Using asymmetrically dividing blood stem cells, we developed a pipeline (ie, trackSeq) for imaging, tracking, isolating, and transcriptome sequencing of single cells. Their identities, kinship, and histories are maintained throughout, massively improving molecular noise filtering and candidate identification. In addition to many identified blood stem CFD regulators, we offer here this pipeline for use in CFDs other than asymmetric division.

中文翻译：

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结合单细胞追踪和组学改进血液干细胞命运调节器识别。

启动细胞命运分歧 (CFD) 的分子程序很难识别。目前的方法通常在 CFD 启动后很久比较细胞，因此在其开始时缺少分子变化。理想情况下，CFD 分子程序不同但其他方面相同的单个细胞会在 CFD 早期进行比较。这在不同的姐妹细胞中是可能的，这些细胞在它们的母亲分裂之前是相同的，因此主要在 CFD 特性上不同。在不对称分裂的细胞中，不同的女儿命运在分裂过程中预期会发生，因此可以在 CFD 开始时识别出不同的姐妹。使用不对称分裂的造血干细胞，我们开发了用于单细胞成像、跟踪、分离和转录组测序的管道（即 trackSeq）。他们的身份、亲属关系，和历史在整个过程中得到维护，极大地改进了分子噪声过滤和候选识别。除了许多已确定的血干 CFD 监管机构外，我们在此提供此管道用于 CFD 而非不对称分割。