PMID- 37232730
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230529
IS  - 1467-3045 (Electronic)
IS  - 1467-3037 (Print)
IS  - 1467-3037 (Linking)
VI  - 45
IP  - 5
DP  - 2023 May 7
TI  - Overexpression of OLIG2 and MYT1L Transcription Factors Enhance the 
      Differentiation Potential of Human Mesenchymal Stem Cells into Oligodendrocytes.
PG  - 4100-4123
LID - 10.3390/cimb45050261 [doi]
AB  - BACKGROUND: Demyelinating diseases represent a broad spectrum of disorders and 
      are characterized by the loss of specialized glial cells (oligodendrocytes), 
      which eventually leads to neuronal degeneration. Stem cell-based regenerative 
      approaches provide therapeutic options to regenerate demyelination-induced 
      neurodegeneration. OBJECTIVES: The current study aims to explore the role of 
      oligodendrocyte-specific transcription factors (OLIG2 and MYT1L) under suitable 
      media composition to facilitate human umbilical-cord-derived mesenchymal stem 
      cells (hUC-MSCs) differentiation toward oligodendrocyte for their potential use 
      to treat demyelinating disorders. METHODOLOGY: hUC-MSCs were isolated, cultured, 
      and characterized based on their morphological and phenotypic characteristics. 
      hUC-MSCs were transfected with OLIG2 and MYT1L transcription factors individually 
      and in synergistic (OLIG2 + MYT1L) groups using a lipofectamine-based 
      transfection method and incubated under two different media compositions (normal 
      and oligo induction media). Transfected hUC-MSCs were assessed for lineage 
      specification and differentiation using qPCR. Differentiation was also analyzed 
      via immunocytochemistry by determining the expression of oligodendrocyte-specific 
      proteins. RESULTS: All the transfected groups showed significant upregulation of 
      GFAP and OLIG2 with downregulation of NES, demonstrating the MSC commitment 
      toward the glial lineage. Transfected groups also presented significant 
      overexpression of oligodendrocyte-specific markers (SOX10, NKX2.2, GALC, CNP, 
      CSPG4, MBP, and PLP1). Immunocytochemical analysis showed intense expression of 
      OLIG2, MYT1L, and NG2 proteins in both normal and oligo induction media after 3 
      and 7 days. CONCLUSIONS: The study concludes that OLIG2 and MYT1L have the 
      potential to differentiate hUC-MSCs into oligodendrocyte-like cells, which is 
      greatly facilitated by the oligo induction medium. The study may serve as a 
      promising cell-based therapeutic strategy against demyelination-induced neuronal 
      degeneration.
FAU - Fahim, Ifrah
AU  - Fahim I
AD  - Dr. Panjwani Center for Molecular Medicine and Drug Research, International 
      Center for Chemical and Biological Sciences, University of Karachi, Karachi 
      75270, Pakistan.
FAU - Ishaque, Aisha
AU  - Ishaque A
AD  - Dr. Panjwani Center for Molecular Medicine and Drug Research, International 
      Center for Chemical and Biological Sciences, University of Karachi, Karachi 
      75270, Pakistan.
FAU - Ramzan, Faiza
AU  - Ramzan F
AD  - Dr. Panjwani Center for Molecular Medicine and Drug Research, International 
      Center for Chemical and Biological Sciences, University of Karachi, Karachi 
      75270, Pakistan.
FAU - Shamsuddin, Shamsul Azlin Bin Ahmad
AU  - Shamsuddin SABA
AUID- ORCID: 0000-0001-7983-6502
AD  - Institute of Biological Sciences, Faculty of Sciences, Universiti Malaya, Kuala 
      Lumpur 50603, Malaysia.
FAU - Ali, Anwar
AU  - Ali A
AD  - Department of Physiology, University of Karachi, Karachi 75270, Pakistan.
FAU - Salim, Asmat
AU  - Salim A
AD  - Dr. Panjwani Center for Molecular Medicine and Drug Research, International 
      Center for Chemical and Biological Sciences, University of Karachi, Karachi 
      75270, Pakistan.
FAU - Khan, Irfan
AU  - Khan I
AUID- ORCID: 0000-0003-1878-7836
AD  - Dr. Panjwani Center for Molecular Medicine and Drug Research, International 
      Center for Chemical and Biological Sciences, University of Karachi, Karachi 
      75270, Pakistan.
LA  - eng
GR  - 6573/Higher Education Commission/
PT  - Journal Article
DEP - 20230507
PL  - Switzerland
TA  - Curr Issues Mol Biol
JT  - Current issues in molecular biology
JID - 100931761
PMC - PMC10217246
OTO - NOTNLM
OT  - differentiation
OT  - fate specification
OT  - gene expression
OT  - mesenchymal stem cells
OT  - oligodendrocytes
COIS- Authors declare no conflict of Interest.
EDAT- 2023/05/26 13:09
MHDA- 2023/05/26 13:10
PMCR- 2023/05/07
CRDT- 2023/05/26 09:33
PHST- 2023/03/14 00:00 [received]
PHST- 2023/04/13 00:00 [revised]
PHST- 2023/05/04 00:00 [accepted]
PHST- 2023/05/26 13:10 [medline]
PHST- 2023/05/26 13:09 [pubmed]
PHST- 2023/05/26 09:33 [entrez]
PHST- 2023/05/07 00:00 [pmc-release]
AID - cimb45050261 [pii]
AID - cimb-45-00261 [pii]
AID - 10.3390/cimb45050261 [doi]
PST - epublish
SO  - Curr Issues Mol Biol. 2023 May 7;45(5):4100-4123. doi: 10.3390/cimb45050261.