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Differentiated cells can be converted into pluripotent stem cells by expressing the transcription factors OCT4, SOX2, KLF4, and MYC (OSKM) in a process known as reprogramming. Here, using single-cell RNA sequencing of pancreas undergoing reprogramming, we identify markers along the trajectory from acinar cell identity to pluripotency. These markers allow direct in situ visualization of cells undergoing dedifferentiation and acquiring features of early and advanced intermediate reprogramming. We also find that a fraction of cells do not dedifferentiate upon OSKM expression and are characterized by stress markers of the REG3 and AP-1 families. Importantly, most markers of intermediate reprogramming in the pancreas are also observed in stomach, colon, and cultured fibroblasts expressing OSKM. Among them is LY6A, a protein characteristic of progenitor cells and generally upregulated during tissue repair. Our roadmap defines intermediate reprogramming states that could be functionally relevant for tissue regeneration and rejuvenation. Work in the laboratory of F.X.R. was funded by grants from the Spanish Ministry of Science co-funded by the ERDF-EU (SAF2015-70553-R and RTI2018-101071-B-I00). Work in the laboratory of M.S. was funded by the IRB and by grants from the Spanish Ministry of Science co-funded by the ERDF-EU (SAF2017-82613-R), European Research Council (ERC-2014-AdG/669622), Secretaria d'Universitats i Recerca del Departament d'Empresa i Coneixement of Catalonia (Grup de Recerca consolidat 2017 SGR 282), “la Caixa” Foundation, and the Milky Way Research Foundation. The CNIO and IRB are supported by the Spanish Ministry of Science as Centres of Excellence “Severo Ochoa.”