Abstract

Understandingtheexactcell-typecompositioninthedifferentregionsofthehumanbrainisafundamentalstep whentryingtointegratephysiological,behavioral,neurochemicalandmoleculardata.Atpresent,although majorcategoriesofcell-typespresentinthehumanbrainhavebeendefinedthroughahandfulofspecific markers,thedifferentsubtypeswithinthesecategoriesaswellastheirlocationarefarfromunderstood. CytosineDNAmethylation(mC)isastableepigenomicsignaturethatpersistsinpost-mitoticcellsthroughout theirlifetime,definingtheircellularidentity.Openchromatinmarksgeneregulatoryelementsthatcontrolcell type-specificgeneexpressionpatterns.SinglecellDNAmethylationandopenchromatinprofileshavebeen successfullyusedtoidentifydenovodistinctcelltypesinheterogeneoustissuesincludingthebrain.ThisU01 aimstoproduceafirstversionofanepigenomiccellatlasatthesingle-celllevelacrossthehumanbrain. Multi-modalintegrationbetweenepigenomicandtranscriptomicsignatureswillallowtheidentificationofnew celltypesanduniquecell-typemarkersthatwillbecomeavailabletothecommunity.Epigenomicprofilingof humanbraincellspermitsthediscoveryofcelltype-specificregulatoryregions,whichwillfacilitatethe functionalanalysisofgeneticvariantsassociatedwithpsychiatricandneurologicaldisorders.

Public Health Relevance

Brainfunctionarisesfromnetworksofcellsconnectedtoeachotherinneuralcircuits.ThegoalofthisU01 projectistounderstandtheidentityofthemanydifferentkindsofcellsinvariousregionsofthehumanbrain. Determiningthecellcompositionofthehumanbrainwillaidintheunderstandingofavarietyofhuman diseasessuchasschizophreniaorautismwheretheseneuralcircuitsmaybeabnormal.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01MH121282-02
Application #
10018649
Study Section
Special Emphasis Panel (ZMH1)
Program Officer
Yao, Yong
Project Start
2019-09-16
Project End
2022-08-31
Budget Start
2020-09-01
Budget End
2021-08-31
Support Year
2
Fiscal Year
2020
Total Cost
Indirect Cost

  Institution

Name
Salk Institute for Biological Studies
Department
Type
DUNS #
078731668
City
La Jolla
State
CA
Country
United States
Zip Code
92037