SUMOylation controls stem cell proliferation and regional cell death through Hedgehog signaling in planarians

Cellular and Molecular Life Sciences : CMLS
Manish ThiruvalluvanNéstor J Oviedo

Abstract

Mechanisms underlying anteroposterior body axis differences during adult tissue maintenance and regeneration are poorly understood. Here, we identify that post-translational modifications through the SUMO (Small Ubiquitin-like Modifier) machinery are evolutionarily conserved in the Lophotrocozoan Schmidtea mediterranea. Disruption of SUMOylation in adult animals by RNA-interference of the only SUMO E2 conjugating enzyme Ubc9 leads to a systemic increase in DNA damage and a remarkable regional defect characterized by increased cell death and loss of the posterior half of the body. We identified that Ubc9 is mainly expressed in planarian stem cells (neoblasts) but it is also transcribed in differentiated cells including neurons. Regeneration in Ubc9(RNAi) animals is impaired and associated with low neoblast proliferation. We present evidence indicating that Ubc9-induced regional cell death is preceded by alterations in transcription and spatial expression of repressors and activators of the Hedgehog signaling pathway. Our results demonstrate that SUMOylation acts as a regional-specific cue to regulate cell fate during tissue renewal and regeneration.

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Citations

Mar 9, 2019·Journal of Cellular Biochemistry·Biying JiangChuifeng Fan
Feb 6, 2020·International Journal of Molecular Sciences·Paul G BarghouthNéstor J Oviedo
Jan 26, 2021·STAR Protocols·Paul G Barghouth, Néstor J Oviedo
Dec 21, 2018·Developmental and Comparative Immunology·Eli Isael MacielNéstor J Oviedo
Mar 29, 2021·Developmental Biology·Susanna FraguasFrancesc Cebrià
May 15, 2021·DNA Repair·Salvador Rojas, Néstor J Oviedo
Jul 14, 2021·Open Biology·Zenghua ShengShufang Liang
Aug 17, 2021·Stem Cells·Claudia Colussi, Claudio Grassi
Jan 12, 2021··Paul G. Barghouth, Néstor J. Oviedo

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Methods Mentioned

BETA
FACS
flow cytometry
electrophoresis
nuclear translocation
amputation
sumoylation
ubiquitination
PCR

Software Mentioned

UNIPROT
MAFFT
FigTree
ProtTest
NIS element
Blastn
ImageJ
Prism
Blastp
PFAM

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