In:
eLife, eLife Sciences Publications, Ltd, Vol. 8 ( 2019-03-12)
Abstract:
Forced transcription factor expression can transdifferentiate somatic cells into other specialised cell types or reprogram them into induced pluripotent stem cells (iPSCs) with variable efficiency. To better understand the heterogeneity of these processes, we used single-cell RNA sequencing to follow the transdifferentation of murine pre-B cells into macrophages as well as their reprogramming into iPSCs. Even in these highly efficient systems, there was substantial variation in the speed and path of fate conversion. We predicted and validated that these differences are inversely coupled and arise in the starting cell population, with Mychigh large pre-BII cells transdifferentiating slowly but reprogramming efficiently and Myclow small pre-BII cells transdifferentiating rapidly but failing to reprogram. Strikingly, differences in Myc activity predict the efficiency of reprogramming across a wide range of somatic cell types. These results illustrate how single cell expression and computational analyses can identify the origins of heterogeneity in cell fate conversion processes.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.41627.001
DOI:
10.7554/eLife.41627.002
DOI:
10.7554/eLife.41627.003
DOI:
10.7554/eLife.41627.004
DOI:
10.7554/eLife.41627.005
DOI:
10.7554/eLife.41627.006
DOI:
10.7554/eLife.41627.007
DOI:
10.7554/eLife.41627.008
DOI:
10.7554/eLife.41627.009
DOI:
10.7554/eLife.41627.010
DOI:
10.7554/eLife.41627.011
DOI:
10.7554/eLife.41627.012
DOI:
10.7554/eLife.41627.013
DOI:
10.7554/eLife.41627.014
DOI:
10.7554/eLife.41627.015
DOI:
10.7554/eLife.41627.016
DOI:
10.7554/eLife.41627.017
DOI:
10.7554/eLife.41627.018
DOI:
10.7554/eLife.41627.019
DOI:
10.7554/eLife.41627.020
DOI:
10.7554/eLife.41627.021
DOI:
10.7554/eLife.41627.022
DOI:
10.7554/eLife.41627.030
DOI:
10.7554/eLife.41627.031
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2019
detail.hit.zdb_id:
2687154-3