SIS-seq, a molecular ‘time machine’, connects single cell fate with gene programs

Luyi, T.; Schreuder, J.; Amann-Zalcenstein, D.; Tran, J.; Kocovski, N.; Su, S.; Diakumis, P.; Bahlo, M.; Sargeant, T.; Ritchie, M.; Hodgkin, P.; Naik, S.

doi:10.1101/403113

bioRxiv · 10.1101/403113

SIS-seq, a molecular ‘time machine’, connects single cell fate with gene programs

Luyi, T.·Schreuder, J.·Amann-Zalcenstein, D.·Tran, J.·Kocovski, N.·Su, S.·Diakumis, P.·Bahlo, M.·Sargeant, T.·Ritchie, M.·Hodgkin, P.·Naik, S.

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Abstract

Conventional single cell RNA-seq methods are destructive, such that a given cell cannot also then be tested for fate and function, without a time machine. Here, we develop a clonal method SIS-seq, whereby single cells are allowed to divide, and progeny cells are assayed separately in SISter conditions; some for fate, others by RNA-seq. By cross-correlating progenitor gene expression with mature cell fate within a clone, and doing this for many clones, we can identify the earliest gene expression signatures of dendritic cell subset development. SIS-seq could be used to study other populations harboring clonal heterogeneity, including stem, reprogrammed and cancer cells to reveal the transcriptional origins of fate decisions.

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Luyi, T., Schreuder, J., Amann-Zalcenstein, D., Tran, J., Kocovski, N., Su, S., Diakumis, P., Bahlo, M., Sargeant, T., Ritchie, M., Hodgkin, P., Naik, S.. 2018-08-29. SIS-seq, a molecular ‘time machine’, connects single cell fate with gene programs. https://doi.org/10.1101/403113

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