Single-cell transcriptomics reconstructs fate conversion from fibroblast to cardiomyocyte

Nature
Ziqing LiuLi Qian

Abstract

Direct lineage conversion offers a new strategy for tissue regeneration and disease modelling. Despite recent success in directly reprogramming fibroblasts into various cell types, the precise changes that occur as fibroblasts progressively convert to the target cell fates remain unclear. The inherent heterogeneity and asynchronous nature of the reprogramming process renders it difficult to study this process using bulk genomic techniques. Here we used single-cell RNA sequencing to overcome this limitation and analysed global transcriptome changes at early stages during the reprogramming of mouse fibroblasts into induced cardiomyocytes (iCMs). Using unsupervised dimensionality reduction and clustering algorithms, we identified molecularly distinct subpopulations of cells during reprogramming. We also constructed routes of iCM formation, and delineated the relationship between cell proliferation and iCM induction. Further analysis of global gene expression changes during reprogramming revealed unexpected downregulation of factors involved in mRNA processing and splicing. Detailed functional analysis of the top candidate splicing factor, Ptbp1, revealed that it is a critical barrier for the acquisition of cardiomyocyte-specific s...Continue Reading

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Datasets Mentioned

BETA
GSE98571

Methods Mentioned

BETA
RNA-seq
PCA
PCR
chip
chips
ChIP-seq
GAM
Assay
flow cytometry

Software Mentioned

SINGuLAR Analysis Toolset Fluidigm )
HC
FASTQC
R package
VGAM R
PCA
ComBat
DAVID
SINGuLAR
DEseq

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