Single-cell lineage capture across genomic modalities with CellTag-multi reveals fate-specific gene regulatory changes.

Autor: Jindal K; Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, USA.; Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.; Center of Regenerative Medicine, Washington University School of Medicine, St. Louis, MO, USA., Adil MT; Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, USA.; Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.; Center of Regenerative Medicine, Washington University School of Medicine, St. Louis, MO, USA., Yamaguchi N; Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, USA.; Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.; Center of Regenerative Medicine, Washington University School of Medicine, St. Louis, MO, USA., Yang X; Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, USA.; Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.; Center of Regenerative Medicine, Washington University School of Medicine, St. Louis, MO, USA., Wang HC; Department of Pediatrics, Division of Hematology and Oncology, Washington University School of Medicine, St. Louis, MO, USA., Kamimoto K; Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, USA.; Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.; Center of Regenerative Medicine, Washington University School of Medicine, St. Louis, MO, USA., Rivera-Gonzalez GC; Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, USA.; Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.; Center of Regenerative Medicine, Washington University School of Medicine, St. Louis, MO, USA., Morris SA; Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, USA. s.morris@wustl.edu.; Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA. s.morris@wustl.edu.; Center of Regenerative Medicine, Washington University School of Medicine, St. Louis, MO, USA. s.morris@wustl.edu.
Jazyk: angličtina
Zdroj: Nature biotechnology [Nat Biotechnol] 2024 Jun; Vol. 42 (6), pp. 946-959. Date of Electronic Publication: 2023 Sep 25.
DOI: 10.1038/s41587-023-01931-4
Abstrakt: Complex gene regulatory mechanisms underlie differentiation and reprogramming. Contemporary single-cell lineage-tracing (scLT) methods use expressed, heritable DNA barcodes to combine cell lineage readout with single-cell transcriptomics. However, reliance on transcriptional profiling limits adaptation to other single-cell assays. With CellTag-multi, we present an approach that enables direct capture of heritable random barcodes expressed as polyadenylated transcripts, in both single-cell RNA sequencing and single-cell Assay for Transposase Accessible Chromatin using sequencing assays, allowing for independent clonal tracking of transcriptional and epigenomic cell states. We validate CellTag-multi to characterize progenitor cell lineage priming during mouse hematopoiesis. Additionally, in direct reprogramming of fibroblasts to endoderm progenitors, we identify core regulatory programs underlying on-target and off-target fates. Furthermore, we reveal the transcription factor Zfp281 as a regulator of reprogramming outcome, biasing cells toward an off-target mesenchymal fate. Our results establish CellTag-multi as a lineage-tracing method compatible with multiple single-cell modalities and demonstrate its utility in revealing fate-specifying gene regulatory changes across diverse paradigms of differentiation and reprogramming.
(© 2023. The Author(s).)
Databáze: MEDLINE
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