Increasing Notch signaling antagonizes PRC2-mediated silencing to promote reprograming of germ cells into neurons.
Cell-fate reprograming is at the heart of development, yet very little is known about the molecular mechanisms promoting or inhibiting reprograming in intact organisms. In theC. elegansgermline, reprograming germ cells into somatic cells requires chromatin perturbation. Here, we describe that such reprograming is facilitated by GLP-1/Notch signaling pathway. This is surprising, since this pathway is best known for maintaining undifferentiated germline stem cells/progenitors. Through a combination of genetics, tissue-specific transcriptome analysis, and functional studies of candidate genes, we uncovered a possible explanation for this unexpected role of GLP-1/Notch. We propose that GLP-1/Notch promotes reprograming by activating specific genes, silenced by the Polycomb repressive complex 2 (PRC2), and identify the conserved histone demethylase UTX-1 as a crucial GLP-1/Notch target facilitating reprograming. These findings have wide implications, ranging from development to diseases associated with abnormal Notch signaling.
Berlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
Stefanie
S
Seelk
Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
Irene
I
Adrian-Kalchhauser
Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
Balázs
B
Hargitai
Berlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
Martina
M
Hajduskova
Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
Silvia
S
Gutnik
Berlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
Baris
http://orcid.org/0000-0001-7293-8629
B
Tursun
Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
Rafal
http://orcid.org/0000-0003-2234-6216
R
Ciosk
C. elegans; Notch; PRC2; T-ALL; developmental biology; germ cell; glp-1; leukemia; mes-2; mes-3; mes-6; reprograming; stem cell; stem cells; utx-1