PMID- 29422555
OWN - NLM
STAT- MEDLINE
DCOM- 20190820
LR  - 20190820
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 8
IP  - 1
DP  - 2018 Feb 8
TI  - Temporal downregulation of the polyubiquitin gene Ubb affects neuronal 
      differentiation, but not maturation, in cells cultured in vitro.
PG  - 2629
LID - 10.1038/s41598-018-21032-6 [doi]
LID - 2629
AB  - Reduced levels of cellular ubiquitin (Ub) pools due to disruption of the 
      polyubiquitin gene Ubb lead to dysregulation of neural stem cell (NSC) 
      differentiation and impaired neuronal maturation in cells isolated from Ubb (-/-) 
      mouse embryonic brains. However, it is currently unknown whether Ub is required 
      for the specific stage of neuronal development or whether it plays a pleiotropic 
      role throughout the process. To answer this question, we aimed to downregulate 
      Ubb expression temporally during neuronal development, which could not be 
      achieved in Ubb (-/-) cells. Therefore, we exploited lentivirus-mediated 
      knockdown (KD) of Ubb at different stages of neuronal development, and 
      investigated their phenotypes. Here, we report the outcome of Ubb KD on two 
      independent culture days in vitro (DIV): DIV1 and DIV7. We observed that NSCs did 
      not differentiate properly via Ubb KD on DIV1, but the maturation of already 
      differentiated neurons was intact via Ubb KD on DIV7. Intriguingly, Ubb KD 
      activated Notch signaling when it had been suppressed, but exerted no effect when 
      it had already been activated. Therefore, our study suggests that Ub plays a 
      pivotal role in NSC differentiation to suppress Notch signaling, but not in the 
      subsequent maturation stages of neurons that had already been differentiated.
FAU - Jung, Byung-Kwon
AU  - Jung BK
AD  - Department of Life Science, University of Seoul, Seoul, 02504, Republic of Korea.
FAU - Park, Chul-Woo
AU  - Park CW
AD  - Department of Life Science, University of Seoul, Seoul, 02504, Republic of Korea.
FAU - Ryu, Kwon-Yul
AU  - Ryu KY
AD  - Department of Life Science, University of Seoul, Seoul, 02504, Republic of Korea. 
      kyryu@uos.ac.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180208
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Receptors, Notch)
RN  - 0 (Ubb protein, mouse)
RN  - 0 (Ubiquitin)
RN  - 120904-94-1 (Polyubiquitin)
MH  - Animals
MH  - Cells, Cultured
MH  - Down-Regulation
MH  - *Gene Expression Regulation
MH  - Mice
MH  - Neural Stem Cells/*cytology
MH  - Neurogenesis/*genetics
MH  - Neurons/*cytology
MH  - Polyubiquitin/metabolism
MH  - Receptors, Notch/metabolism
MH  - Signal Transduction
MH  - Ubiquitin/*genetics
PMC - PMC5805694
COIS- The authors declare no competing interests.
EDAT- 2018/02/10 06:00
MHDA- 2019/08/21 06:00
PMCR- 2018/02/08
CRDT- 2018/02/10 06:00
PHST- 2017/05/08 00:00 [received]
PHST- 2018/01/29 00:00 [accepted]
PHST- 2018/02/10 06:00 [entrez]
PHST- 2018/02/10 06:00 [pubmed]
PHST- 2019/08/21 06:00 [medline]
PHST- 2018/02/08 00:00 [pmc-release]
AID - 10.1038/s41598-018-21032-6 [pii]
AID - 21032 [pii]
AID - 10.1038/s41598-018-21032-6 [doi]
PST - epublish
SO  - Sci Rep. 2018 Feb 8;8(1):2629. doi: 10.1038/s41598-018-21032-6.