PMID- 32669437
OWN - NLM
STAT- MEDLINE
DCOM- 20200917
LR  - 20211204
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 117
IP  - 30
DP  - 2020 Jul 28
TI  - Regulation of stem cell function and neuronal differentiation by HERV-K via mTOR 
      pathway.
PG  - 17842-17853
LID - 10.1073/pnas.2002427117 [doi]
AB  - Stem cells are capable of unlimited proliferation but can be induced to form 
      brain cells. Factors that specifically regulate human development are poorly 
      understood. We found that human stem cells expressed high levels of the envelope 
      protein of an endogenized human-specific retrovirus (HERV-K, HML-2) from loci in 
      chromosomes 12 and 19. The envelope protein was expressed on the cell membrane of 
      the stem cells and was critical in maintaining the stemness via interactions with 
      CD98HC, leading to triggering of human-specific signaling pathways involving 
      mammalian target of rapamycin (mTOR) and lysophosphatidylcholine acyltransferase 
      (LPCAT1)-mediated epigenetic changes. Down-regulation or epigenetic silencing of 
      HML-2 env resulted in dissociation of the stem cell colonies and enhanced 
      differentiation along neuronal pathways. Thus HML-2 regulation is critical for 
      human embryonic and neurodevelopment, while it's dysregulation may play a role in 
      tumorigenesis and neurodegeneration.
FAU - Wang, Tongguang
AU  - Wang T
AUID- ORCID: 0000-0003-0195-5661
AD  - Translational Neuroscience Center, National Institute of Neurological Disorders 
      and Stroke, National Institutes of Health, Bethesda, MD 20892.
FAU - Medynets, Marie
AU  - Medynets M
AD  - Translational Neuroscience Center, National Institute of Neurological Disorders 
      and Stroke, National Institutes of Health, Bethesda, MD 20892.
FAU - Johnson, Kory R
AU  - Johnson KR
AD  - Bioinformatics Section, National Institute of Neurological Disorders and Stroke, 
      National Institutes of Health, Bethesda, MD 20892.
FAU - Doucet-O'Hare, Tara T
AU  - Doucet-O'Hare TT
AD  - Section of Infections of the Nervous System, National Institute of Neurological 
      Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
FAU - DiSanza, Brianna
AU  - DiSanza B
AD  - Section of Infections of the Nervous System, National Institute of Neurological 
      Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
FAU - Li, Wenxue
AU  - Li W
AD  - Section of Infections of the Nervous System, National Institute of Neurological 
      Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
FAU - Xu, Yadi
AU  - Xu Y
AD  - Section of Infections of the Nervous System, National Institute of Neurological 
      Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
FAU - Bagnell, Anna
AU  - Bagnell A
AUID- ORCID: 0000-0002-8469-0154
AD  - Translational Neuroscience Center, National Institute of Neurological Disorders 
      and Stroke, National Institutes of Health, Bethesda, MD 20892.
FAU - Tyagi, Richa
AU  - Tyagi R
AD  - Section of Infections of the Nervous System, National Institute of Neurological 
      Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
FAU - Sampson, Kevon
AU  - Sampson K
AD  - Section of Infections of the Nervous System, National Institute of Neurological 
      Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
FAU - Malik, Nasir
AU  - Malik N
AD  - Translational Neuroscience Center, National Institute of Neurological Disorders 
      and Stroke, National Institutes of Health, Bethesda, MD 20892.
FAU - Steiner, Joseph
AU  - Steiner J
AD  - Translational Neuroscience Center, National Institute of Neurological Disorders 
      and Stroke, National Institutes of Health, Bethesda, MD 20892.
FAU - Hadegan, Alina
AU  - Hadegan A
AD  - Section of Infections of the Nervous System, National Institute of Neurological 
      Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
FAU - Kowalak, Jeffrey
AU  - Kowalak J
AD  - Translational Neuroscience Center, National Institute of Neurological Disorders 
      and Stroke, National Institutes of Health, Bethesda, MD 20892.
FAU - O'Malley, James
AU  - O'Malley J
AD  - Animal Health and Care Section, National Institute of Neurological Disorders and 
      Stroke, National Institutes of Health, Bethesda, MD 20892.
FAU - Maric, Dragan
AU  - Maric D
AD  - Flow and Imaging Cytometry Core Facility, National Institute of Neurological 
      Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
FAU - Nath, Avindra
AU  - Nath A
AUID- ORCID: 0000-0003-0927-5855
AD  - Translational Neuroscience Center, National Institute of Neurological Disorders 
      and Stroke, National Institutes of Health, Bethesda, MD 20892; 
      natha@ninds.nih.gov.
AD  - Section of Infections of the Nervous System, National Institute of Neurological 
      Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20200715
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Biomarkers)
RN  - 0 (Fusion Regulatory Protein 1, Heavy Chain)
RN  - 0 (SLC3A2 protein, human)
RN  - 0 (Transcription Factors)
RN  - 0 (Viral Envelope Proteins)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Biomarkers
MH  - *Cell Differentiation/genetics
MH  - Cell Self Renewal/genetics
MH  - Endogenous Retroviruses/*physiology
MH  - Fusion Regulatory Protein 1, Heavy Chain/metabolism
MH  - Gene Expression Regulation, Viral
MH  - Humans
MH  - Induced Pluripotent Stem Cells/cytology/metabolism
MH  - Neural Stem Cells/cytology/metabolism
MH  - Neurons/cytology/*metabolism
MH  - Protein Binding
MH  - *Signal Transduction
MH  - Stem Cells/cytology/*metabolism
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Transcription Factors/genetics/metabolism
MH  - Viral Envelope Proteins/genetics
PMC - PMC7395438
OTO - NOTNLM
OT  - embryogenesis
OT  - endogenous retrovirus
OT  - neurogenesis
OT  - progenitor cells
OT  - stem cells
COIS- The authors declare no competing interest.
EDAT- 2020/07/17 06:00
MHDA- 2020/09/18 06:00
PMCR- 2021/01/15
CRDT- 2020/07/17 06:00
PHST- 2020/07/17 06:00 [pubmed]
PHST- 2020/09/18 06:00 [medline]
PHST- 2020/07/17 06:00 [entrez]
PHST- 2021/01/15 00:00 [pmc-release]
AID - 2002427117 [pii]
AID - 202002427 [pii]
AID - 10.1073/pnas.2002427117 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2020 Jul 28;117(30):17842-17853. doi: 
      10.1073/pnas.2002427117. Epub 2020 Jul 15.