Asymmetric Cell Division of Fibroblasts is An Early Deterministic Step to Generate Elite Cells during Cell Reprogramming

Yang Song, Jennifer Soto, Pingping Wang, Qin An, Xuexiang Zhang, Soon Gweon Hong, Luke P. Lee, Guoping Fan, Li Yang, Song Li

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Cell reprogramming is considered a stochastic process, and it is not clear which cells are prone to be reprogrammed and whether a deterministic step exists. Here, asymmetric cell division (ACD) at the early stage of induced neuronal (iN) reprogramming is shown to play a deterministic role in generating elite cells for reprogramming. Within one day, fibroblasts underwent ACD, with one daughter cell being converted into an iN precursor and the other one remaining as a fibroblast. Inhibition of ACD significantly inhibited iN conversion. Moreover, the daughter cells showed asymmetric DNA segregation and histone marks during cytokinesis, and the cells inheriting newly replicated DNA strands during ACD became iN precursors. These results unravel a deterministic step at the early phase of cell reprogramming and demonstrate a novel role of ACD in cell phenotype change. This work also supports a novel hypothesis that daughter cells with newly replicated DNA strands are elite cells for reprogramming, which remains to be tested in various reprogramming processes.

Original languageEnglish
Article number2003516
JournalAdvanced Science
Volume8
Issue number7
DOIs
StatePublished - 7 Apr 2021

Bibliographical note

Publisher Copyright:
© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH

Keywords

  • asymmetric cell division
  • cell fate determination
  • direct reprogramming
  • epigenetic state

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