Resolving Cell Fate Decisions during Somatic Cell Reprogramming by Single-Cell RNA-Seq.
Mol Cell
; 73(4): 815-829.e7, 2019 02 21.
Article
in En
| MEDLINE
| ID: mdl-30772174
ABSTRACT
Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs), which is a highly heterogeneous process. Here we report the cell fate continuum during somatic cell reprogramming at single-cell resolution. We first develop SOT to analyze cell fate continuum from Oct4/Sox2/Klf4- or OSK-mediated reprogramming and show that cells bifurcate into two categories, reprogramming potential (RP) or non-reprogramming (NR). We further show that Klf4 contributes to Cd34+/Fxyd5+/Psca+ keratinocyte-like NR fate and that IFN-γ impedes the final transition to chimera-competent pluripotency along the RP cells. We analyze more than 150,000 single cells from both OSK and chemical reprograming and identify additional NR/RP bifurcation points. Our work reveals a generic bifurcation model for cell fate decisions during somatic cell reprogramming that may be applicable to other systems and inspire further improvements for reprogramming.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cell Differentiation
/
Sequence Analysis, RNA
/
Cell Lineage
/
Cellular Reprogramming
/
Induced Pluripotent Stem Cells
/
Single-Cell Analysis
/
Mouse Embryonic Stem Cells
/
Cellular Reprogramming Techniques
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Mol Cell
Year:
2019
Document type:
Article