Epigenetics research opens potential door to prevent neurodevelopmental disorders

Sai Ma, for­mer Vir­ginia Tech bio­med­ical engi­neer­ing Ph.D. stu­dent, and Chang Lu, the Fred W. Bull pro­fes­sor of Chem­i­cal Engi­neer­ing at Vir­ginia Tech. Cred­it: Vir­ginia Tech

___

Epi­ge­net­ic Changes Guide Devel­op­ment of Dif­fer­ent Brain Regions (Dana Foundation):

“It’s one of the great­est stand­ing mys­ter­ies in neu­ro­science: Giv­en that each cell in the human body con­tains the same DNA, how, exact­ly, does the brain devel­op into dis­tinct func­tion­al regions, sup­port­ed by dif­fer­ent cell types? And how might that devel­op­men­tal pro­gram go awry, result­ing in neu­rode­vel­op­men­tal dis­or­ders like schiz­o­phre­nia or autism? The answers may be the epigenome, or pro­gram of spe­cif­ic DNA mod­i­fi­ca­tions that affect where, when, and how much a par­tic­u­lar gene will be expressed. Researchers at Vir­ginia Poly­tech­nic Insti­tute and State Uni­ver­si­ty (Vir­ginia Tech) have recent­ly dis­cov­ered sig­nif­i­cant epi­ge­net­ic dif­fer­ences when com­par­ing cells in the cere­bel­lum and the pre­frontal cor­tex of the mouse brain … West says. “The cere­bel­lum devel­ops after birth and it’s entire­ly pos­si­ble that its orga­ni­za­tion is more vul­ner­a­ble to cer­tain kind of insults—insults that can affect the brain’s over­all cir­cuit­ry. Maybe there is some com­mon bio­log­i­cal process, some change to the epigenome, that results in the kind of prob­lems we see in neu­rode­vel­op­men­tal disorders” …

“If we can under­stand the genet­ics and the epi­ge­net­ics of the healthy brain—and then what’s dif­fer­ent in a vari­ety of neu­ro­log­i­cal or neu­ropsy­chi­atric dis­eases, we’ll be in a posi­tion to use these new tech­nolo­gies to inter­vene in the cir­cuit­ry before things go wrong,” he (Chang Lu, chem­i­cal engi­neer at Vir­ginia Tech) says. “This could lead to dis­cov­er­ies that are of direct clin­i­cal relevance.”

The Study:

Low-input and mul­ti­plexed microflu­idic assay reveals epige­nom­ic vari­a­tion across cere­bel­lum and pre­frontal cor­tex (Sci­enceAd­vances)

• Abstract: Exten­sive effort is under way to sur­vey the epige­nom­ic land­scape of pri­ma­ry ex vivo tis­sues to estab­lish nor­mal ref­er­ence data and to dis­cern vari­a­tion asso­ci­at­ed with dis­ease. The low abun­dance of some tis­sue types and the iso­la­tion pro­ce­dure required to gen­er­ate a homoge­nous cell pop­u­la­tion often yield a small quan­ti­ty of cells for exam­i­na­tion. This dif­fi­cul­ty is fur­ther com­pound­ed by the need to pro­file a myr­i­ad of epi­ge­net­ic marks. Thus, tech­nolo­gies that per­mit both ultralow input and high through­put are desired. We demon­strate a sim­ple microflu­idic tech­nol­o­gy, Sur­faceChIP-seq, for pro­fil­ing genome-wide his­tone mod­i­fi­ca­tions using as few as 30 to 100 cells per assay and with up to eight assays run­ning in par­al­lel. We applied the tech­nol­o­gy to pro­file epigenomes using nuclei iso­lat­ed from pre­frontal cor­tex and cere­bel­lum of mouse brain. Our cell type–specific data revealed that neu­ronal and glial frac­tions exhib­it­ed pro­found epige­nom­ic dif­fer­ences across the two func­tion­al­ly dis­tinct brain regions.

The Study in Context:

• Under­stand your con­nec­tome, under­stand yourself
• A new era of brain car­tog­ra­phy, pow­ered by neu­roimag­ing and machine learning
• Study: Both mater­nal and parental obe­si­ty linked to young children’s neu­rode­vel­op­men­tal delays
• Large study to study impact on ear­ly brain devel­op­ment of finan­cial assis­tance to low-income mothers