Single-cell mapping of lineage and identity in direct reprogramming

Brent A. Biddy, Wenjun Kong, Kenji Kamimoto, Chuner Guo, Sarah E. Waye, Tao Sun, Samantha A. Morris

Research output: Contribution to journalArticle

41 Scopus citations


Direct lineage reprogramming involves the conversion of cellular identity. Single-cell technologies are useful for deconstructing the considerable heterogeneity that emerges during lineage conversion. However, lineage relationships are typically lost during cell processing, complicating trajectory reconstruction. Here we present ‘CellTagging’, a combinatorial cell-indexing methodology that enables parallel capture of clonal history and cell identity, in which sequential rounds of cell labelling enable the construction of multi-level lineage trees. CellTagging and longitudinal tracking of fibroblast to induced endoderm progenitor reprogramming reveals two distinct trajectories: one leading to successfully reprogrammed cells, and one leading to a ‘dead-end’ state, paths determined in the earliest stages of lineage conversion. We find that expression of a putative methyltransferase, Mettl7a1, is associated with the successful reprogramming trajectory; adding Mettl7a1 to the reprogramming cocktail increases the yield of induced endoderm progenitors. Together, these results demonstrate the utility of our lineage-tracing method for revealing the dynamics of direct reprogramming.

Original languageEnglish
Pages (from-to)219-224
Number of pages6
Issue number7735
StatePublished - Dec 13 2018

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    Biddy, B. A., Kong, W., Kamimoto, K., Guo, C., Waye, S. E., Sun, T., & Morris, S. A. (2018). Single-cell mapping of lineage and identity in direct reprogramming. Nature, 564(7735), 219-224.