Genes help in un­der­stand­ing how our liver func­tions – Re­search

Sunday Trust - - NEWS HEALTH - Source:https://www. sci­

If you get up in the morn­ing feeling en­er­getic and clear­headed, you can thank your liver for man­u­fac­tur­ing glu­cose be­fore break­fast time. Among a host of other vi­tal func­tions, it also clears our body of tox­ins and pro­duces most of the car­rier pro­teins in our blood. In a study re­ported re­cently in Na­ture, Weiz­mann In­sti­tute of Sci­ence re­searchers showed that the liver’s amaz­ing mul­ti­task­ing ca­pac­ity is due at least in part to a clever divi­sion of labour among its cells.

Each of the liver’s mi­cro­scopic, hexag­o­nal lob­ules con­sists of onion-like con­cen­tric lay­ers. By map­ping gene ac­tiv­ity in all the cells of a liver lob­ule, Dr. Shalev Itzkovitz of Weiz­mann’s Molec­u­lar Cell Bi­ol­ogy De­part­ment and his re­search team have re­vealed that these lay­ers each per­form dif­fer­ent func­tions. Itzkovitz says: “We’ve found that livuer cells can be di­vided into at least nine dif­fer­ent types, each spe­cial­iz­ing in its own tasks.”

The sci­en­tists found, for in­stance, that the syn­the­sis of glu­cose, blood-clot­ting fac­tors and var­i­ous other ma­te­ri­als takes place in the outer lay­ers of the liver lob­ule. “These lay­ers are rich in the oxy­gen needed to fuel these costly syn­the­sis pro­cesses,” ex­plains Itzkovitz.

The in­ner lay­ers of the liver lob­ules re­vealed them­selves to be the sites where tox­ins and other sub­stances are bro­ken down. The mid­dle lay­ers also proved to have their own func­tions, rather than serv­ing as mere transition zones: The re­searchers found, for ex­am­ple, that cells in these lay­ers man­u­fac­ture the hor­mone hep­cidin, which reg­u­lates iron lev­els in the blood.

The sci­en­tists also dis­cov­ered that cer­tain pro­cesses, such as the man­u­fac­ture of bile, pro­ceed across sev­eral dif­fer­ent lay­ers, in some­thing like a pro­duc­tion line.

These dis­cov­er­ies emerged when the re­searchers cre­ated a spa­tial at­las of gene ex­pres­sion for all liver cells, the first of its kind for this or­gan. In col­lab­o­ra­tion with Prof. Ido Amit of Weiz­mann’s Im­munol­ogy De­part­ment, they an­a­lyzed the genomes of 1,500 in­di­vid­ual liver cells, es­tab­lish­ing pat­terns of ex­pres­sion for about 20,000 genes in each cell. In par­al­lel they vi­su­al­ized in­tact liver tis­sue, lo­cat­ing in­di­vid­ual mes­sen­ger RNA mol­e­cules un­der a flu­o­res­cence mi­cro­scope, us­ing a method de­vel­oped by Itzkovitz and his col­leagues. Spe­cial al­go­rithms then en­abled the re­searchers to es­tab­lish both the gene ex­pres­sion in each cell and the lo­ca­tion of these cells in the liver lob­ule. They found that more than half of the 7,000 genes ex­pressed in the liver vary in ac­tiv­ity from one layer to an­other, a num­ber that is about ten times greater than pre­vi­ous es­ti­mates.

Such an in-depth anal­y­sis of gene ex­pres­sion may help clar­ify the course and ori­gin of com­mon liver dis­or­ders, in­clud­ing liver can­cer and non-al­co­holic fatty liver dis­ease, which af­fects about a fifth of the pop­u­la­tion in de­vel­oped coun­tries. In ad­di­tion the ap­proach de­vel­oped in the new study may now be ap­plied to map gene ex­pres­sion else­where in the body.

This is a cross sec­tion of a mouse liver lob­ule un­der a flu­o­res­cence mi­cro­scope. The mid­dle layer re­veals an abun­dance of mes­sen­ger RNA mol­e­cules (white dots) for the gene en­cod­ing hep­cidin, the iron-reg­u­lat­ing hor­mone Credit: Weiz­mann In­sti­tute of Sci­ence

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