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E u r o S c i C o n C o n f e r e n c e o n
Neurology & Neurological
Disorders
Neurology 2018
J u l y 1 2 - 1 3 , 2 0 1 8
P a r i s , F r a n c e
Page 106
Journal of Neurology and Neuroscience
ISSN: 2171-6625
M
icroglia, the native sculptors of neuronal circuits perform various crucial functions in brain milieu, including dendritic pruning,
immune surveillance, phagocytizing of dead neurons and healthy neural precursors etc. In spite of these attributes, several
unresolved queries exist around biomarker discovery relevant to their cellular localization, self-renewing potential and brain
developmental dynamics. To ascertain microglial biomarkers in developing brain, we performed high-throughput data mining of
microglia gene expression datasets. The analysis revealed a list of 3290 significant genes, out of which we have selected the top
20 dysregulated genes to be the potential markers that can be used for tracking the microglial expression in developing brain.
Next, we developed a connectome of these biomarkers with their putative protein interacting partners. This demonstrated strong
associations of upregulated genes like DOCK2 with early/mature microglial markers such as SPHK1, CD68 and CD45. To elucidate
their anatomical habitance, we deconvoluted the BrainSpan Atlas expression data, which showed high level of expression of
majority of candidate genes in microglia-dense regions (Amygdala, Hippocampus, Striatum) in the postnatal brain. Furthermore
to decipher their age specific expression in human brain, we constructed a developmental dynamics map (DDM), we again
deconvoluted gene expression profiles spanning prenatal to postnatal stages. Interestingly, dynamic regulation of SPHK1, PLD4
along with consistent expression of PTX3, FCAR and KLHL6 were detected. To authenticate these findings and correlate their
expressions in vitro, we enforced microglial differentiation to hESC to generate microglia precursors. These microglia precursors
could demonstrate expression of PTX3 and SPHK1 as well as other early stage markers, such as CD68, AIF1 (Iba1) post 30 days
in vitro. In summary, our study has unraveled critical insights regarding microglial expression dynamics across the brain ages and
catalogued a unique set of potential biomarkers those can be further exploited for designing of novel neurotherapeutics.
Soumya.pati@snu.edu.inUnscrambling the epitome of human microglial
gene expression dynamics during brain
development for potential biomarker discovery
R Ayana
1
, Shailja Singh
1,2
and Soumya Pati
1
1
Shiv Nadar University, Uttar Pradesh, India
2
Jawaharlal Nehru University, New Delhi, India
J Neurol Neurosci 2018, Volume: 9
DOI: 10.21767/2171-6625-C1-009