PMID- 34769484
OWN - NLM
STAT- MEDLINE
DCOM- 20220111
LR  - 20220111
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 21
DP  - 2021 Nov 8
TI  - A Novel Isogenic Human Cell-Based System for MEN1 Syndrome Generated by 
      CRISPR/Cas9 Genome Editing.
LID - 10.3390/ijms222112054 [doi]
LID - 12054
AB  - Multiple endocrine neoplasia type 1 (MEN1) is a rare tumor syndrome that 
      manifests differently among various patients. Despite the mutations in the MEN1 
      gene that commonly predispose tumor development, there are no obvious 
      phenotype-genotype correlations. The existing animal and in vitro models do not 
      allow for studies of the molecular genetics of the disease in a human-specific 
      context. We aimed to create a new human cell-based model, which would consider 
      the variability in genetic or environmental factors that cause the complexity of 
      MEN1 syndrome. Here, we generated patient-specific induced pluripotent stem cell 
      lines carrying the mutation c.1252G>T, D418Y in the MEN1 gene. To reduce the 
      genetically determined variability of the existing cellular models, we created an 
      isogenic cell system by modifying the target allele through CRISPR/Cas9 editing 
      with great specificity and efficiency. The high potential of these cell lines to 
      differentiate into the endodermal lineage in defined conditions ensures the next 
      steps in the development of more specialized cells that are commonly affected in 
      MEN1 patients, such as parathyroid or pancreatic islet cells. We anticipate that 
      this isogenic system will be broadly useful to comprehensively study MEN1 gene 
      function across different contexts, including in vitro modeling of MEN1 syndrome.
FAU - Klementieva, Natalia
AU  - Klementieva N
AUID- ORCID: 0000-0002-2742-372X
AD  - Endocrinology Research Centre, 115478 Moscow, Russia.
FAU - Goliusova, Daria
AU  - Goliusova D
AUID- ORCID: 0000-0003-2837-8868
AD  - Vavilov Institute of General Genetics, Russian Academy of Sciences, 119991 
      Moscow, Russia.
FAU - Krupinova, Julia
AU  - Krupinova J
AD  - Endocrinology Research Centre, 115478 Moscow, Russia.
FAU - Yanvarev, Vladislav
AU  - Yanvarev V
AUID- ORCID: 0000-0001-9896-6257
AD  - Vavilov Institute of General Genetics, Russian Academy of Sciences, 119991 
      Moscow, Russia.
FAU - Panova, Alexandra
AU  - Panova A
AD  - Endocrinology Research Centre, 115478 Moscow, Russia.
AD  - Vavilov Institute of General Genetics, Russian Academy of Sciences, 119991 
      Moscow, Russia.
FAU - Mokrysheva, Natalia
AU  - Mokrysheva N
AD  - Endocrinology Research Centre, 115478 Moscow, Russia.
FAU - Kiselev, Sergey L
AU  - Kiselev SL
AD  - Endocrinology Research Centre, 115478 Moscow, Russia.
AD  - Vavilov Institute of General Genetics, Russian Academy of Sciences, 119991 
      Moscow, Russia.
LA  - eng
GR  - 19-015-00209 a/Russian Foundation for Basic Research/
PT  - Journal Article
DEP - 20211108
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (MEN1 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Adult
MH  - CRISPR-Cas Systems
MH  - Cells, Cultured
MH  - Female
MH  - Fibroblasts/*metabolism
MH  - Gene Editing/*methods
MH  - Humans
MH  - Induced Pluripotent Stem Cells/*metabolism
MH  - Multiple Endocrine Neoplasia Type 1/genetics/metabolism/*pathology
MH  - *Mutation
MH  - Proto-Oncogene Proteins/*antagonists & inhibitors/genetics
PMC - PMC8584395
OTO - NOTNLM
OT  - CRISPR/Cas9 genome editing
OT  - MEN1
OT  - definitive endoderm differentiation
OT  - induced pluripotent stem cells
OT  - isogenic cell lines
COIS- The authors declare no conflict of interest.
EDAT- 2021/11/14 06:00
MHDA- 2022/01/12 06:00
PMCR- 2021/11/08
CRDT- 2021/11/13 01:06
PHST- 2021/09/19 00:00 [received]
PHST- 2021/10/27 00:00 [revised]
PHST- 2021/11/04 00:00 [accepted]
PHST- 2021/11/13 01:06 [entrez]
PHST- 2021/11/14 06:00 [pubmed]
PHST- 2022/01/12 06:00 [medline]
PHST- 2021/11/08 00:00 [pmc-release]
AID - ijms222112054 [pii]
AID - ijms-22-12054 [pii]
AID - 10.3390/ijms222112054 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Nov 8;22(21):12054. doi: 10.3390/ijms222112054.