Resolution of Reprogramming Transition States by Single Cell RNA-Sequencing
Abstract
The Yamanaka factors convert mouse embryonic fibroblasts (MEFs) into induced pluripotent stem cells (iPSCs) through a highly heterogeneous process. Here we profile single cells undergoing an optimized 7-day reprogramming process and show that cells start reprogramming relatively in sync, but diverge into two branches around day 2. The first branch of cells expressing Cd34/Fxyd5/Psca become nonpluripotent. The second one contains cells that are first Oct4+, then Dppa5a+ and pluripotent. We show that IFN-γ blocks this late transition. Our results reveal the heterogeneous nature of somatic cell reprogramming, identify Dppa5a as a marker for pluripotent and innate immunity as a potential barrier for reprogramming.
One Sentence Summary Single cell RNA sequencing reveals a continuum of cell fates from somatic to pluripotent and Dppa5a as a marker for chimera-competent iPSCs.
Subject Area
- Biochemistry (11730)
- Bioengineering (8743)
- Bioinformatics (29179)
- Biophysics (14964)
- Cancer Biology (12080)
- Cell Biology (17399)
- Clinical Trials (138)
- Developmental Biology (9417)
- Ecology (14174)
- Epidemiology (2067)
- Evolutionary Biology (18294)
- Genetics (12233)
- Genomics (16791)
- Immunology (11858)
- Microbiology (28051)
- Molecular Biology (11575)
- Neuroscience (60919)
- Paleontology (451)
- Pathology (1870)
- Pharmacology and Toxicology (3238)
- Physiology (4955)
- Plant Biology (10422)
- Synthetic Biology (2881)
- Systems Biology (7338)
- Zoology (1650)