Nat Med | Njira yokhotakhota yochotsera chotupa

Nat Med | Njira yokhotakhota yotupa, mawonekedwe ang'onoang'ono ndi microbial khansa ya colorectil imavumbula kulumikizana kwa microbiiome ndi chitetezo cha mthupi
Ngakhale kuti biloarkers ya khansa yapamwamba ya m'matumbo yakhala ikuphunziridwa kwambiri m'zaka zaposachedwa, malangizo omwe amachitika chifukwa cha chotupa chokhacho. Ofufuzawo adazindikira kuti alibe mayanjano osiyanasiyana, mayankho a microbial, ndi chotupa champhamvu kwambiri ku Atlas atlas (TCGA) kupulumuka kwa odwala.

Monga kafukufuku wapita patsogolo, kuphatikiza khansa yapamwamba kwambiri, koma kumvetsetsa kwa khansa, koma kumvetsetsa pang'ono za momwe zomwe amazichitira zimathandizira kuleza.
Kuti muchepetse ubale pakati pa phenotypic kuvuta ndi zotsatira, gulu la ofufuza kuchokera ku Sidra Institute Pukuda lazakudya mu quatar posachedwapa (ma microsore) omwe amaphatikizidwa (ma microsore) omwe amapereka (ICR). Gululi lidachita kusanthula kokwanira kwa odwala owundana mwatsopano kuchokera kwa odwala 348 okhala ndi khansa yapamwamba kwambiri, kuphatikizapo ma rone otupa a genoretery, zotupa zonse, zotupa zonse zotupa zoyatsa microbi. Kafukufukuyu adasindikizidwa mu chilengedwe ndi "chotupa cholumikizira, chitetezo cha chitetezo cha atlas atlas a khansa ya m'matumbo".
Nkhani yofalitsidwa munthawi yachilengedwe

Nkhani yofalitsidwa munthawi yachilengedwe

AC-ICAM

Ofufuzawo adagwiritsa ntchito nsanja ya mafuta orthogonal kuti afufuze zitsanzo zatsopano zotsetsereka komanso zotupa zapamwamba (zotupa) kuchokera kwa odwala omwe ali ndi vuto la khansa ya m'matumbo popanda chithandizo chamankhwala. Kutengera zingwe zopambana (Wes), RNA DZIKO LAPANSI Gulu lofufuzira linatchedwa comra-lumc ac. mapu ndi chitsogozo cha khansa yonyamula khansa yopanda ntchito (Chithunzi 1).

Kugawa kwa maselo ogwiritsa ntchito ICR

Kulanda kwa ma genetic tortic torkic accorking khansa yosakhala khansa yopitilira, yotchedwa Rusednt offir (iCR), gulu lofufuzira, kuphatikiza ndi khansa ya chikhodzodzo, ndi khansa ya m'mawere, ndi khansa ya m'mawere, ndi khansa ya m'mawere, ndi khansa ya m'mawere, ndi khansa ya m'mawere, ndi khansa ya m'mawere, ndi khansa ya m'mawere, ndi khansa ya m'mawere, ndi khansa ya m'mawere, ndi khansa ya m'mawere, ndi khansa ya m'mawere, ndi khansa ya m'mawere, ndi khansa ya m'mawere, ndi khansa ya m'mawere, ndi khansa ya m'mawere, ndi khansa ya m'mawere, ndi khansa ya m'mawere, ndi khansa ya m'mawere, ndi khansa ya m'mawere, ndi khansa ya m'mawere, ndi khansa ya m'mawere, ndi khansa ya m'mawere, ndi khansa ya m'mawere, ndi khansa ya m'mawere, ndi khansa ya m'mawere, ndi khansa ya m'mawere, ndi khansa ya m'mawere, ndi khansa ya m'mawere, ndi khansa ya m'mawere, ndi khansa ya m'mawere, ndi khansa ya m'mawere, ndi khansa ya m'mawere, ndi khansa ya m'mawere, ndi khansa yamadzi. ICR yakhalanso yolumikizidwa ndi immunotheray yankho lamitundu yambiri, kuphatikizapo khansa ya m'mawere.

Choyamba, ofufuzawo adawonetsa kuti siginecha ya IC-ICAM, pogwiritsa ntchito njira yolumikizirana ndi ICR yomwe imatchulidwa kuti ndi mabatani atatu a mabatani atatu. Ofufuzawo amadziwika kuti ndi luso la chitetezo cholumikizidwa ndi ma couleculas ma subypes (ma cms), gulu lophatikizira la khansa ya m'matumbo. Magawo a CMS adaphatikizapo ma cms1 / camne, cms2 / cananical, cms3 / metabolic ndi cms4 / mensenchnchnmal. Kusanthula kunawonetsa kuti ICR ambiri anali ophatikizidwa ndi ma cell a khansa ku CMS, ndi njira zabwino zokhala ndi njira zokhudzana ndi immunosulal zomwe zimawonedwa kokha m'matumbo a cms4.

M'mitundu yonse, kuchuluka kwa wachilengedwe (NK) maselo ang'onoang'ono kwambiri ku ICR Curmpes, ndi kusinthika kwakukulu mu quukocyte ntersets (Chithunzi 1C), kutsimikizira gawo la kachilomboka kochepa kwambiri.

1

Chithunzi 1. Mapangidwe a AC-ICAM School, kapena siginecha yokhudzana ndi mitundu, yasayansi komanso kupulumuka.
Icr agwira ntchito yotupa, yomwe imply Trewonetsedwa
Ma cell ochepa okha a T amasungunuka minyewa yotupa akadanenedwa kuti azikhala achindunji a argens otupa (ochepera 10%). Chifukwa chake, maselo ambiri a intra-chotupa amatchedwa ma cell a Tys (ma celly T). Kuphatikiza kwamphamvu ndi kuchuluka kwa maselo wamba kwa T ndi masamba ophatikizika amawonedwa mu ma stramal cell ndi leukoculations (zopezeka ndi RNA-seq), zomwe zingagwiritsidwe ntchito kuwerengera maselo (Chithunzi 2A). Mu ICR STUSTER (Consell ndi CMMS Class), okwera kwambiri a TCR TCRS SUQS adawonedwa mu ICR SUBMSP BYYPPE CMYPE CMYPE CMYPE Kugwiritsa ntchito ma transcriptome onse (majini 18,270), ICR itatu) (RAFY isanu ndi umodzi (iff, stat1, Irf1, GZL5, GZLL10) anali mgulu la Sheq (Chithunzi 2d). Immunoseq Tcr Clonecy mogwirizana kwambiri ndi icr majini ambiri kuposa kuphatikiza kwa otupa a CD8 + (Chithunzi 2F ndi 2G). Pomaliza, kusanthula pamwambapa kukusonyeza kuti siginecha ya ICR yomwe imapangitsa kukhalapo kwa chotupa, kutulitsidwa kwa T nthawi zonse ndipo mutha kufotokozera zakuda zomwe zimachitika.
2
Chithunzi 2. Tcr Metrics ndi kuphatikiza ndi majini ang'onoang'ono okhudzana ndi ndalama, osakhazikika komanso subypel studypes.
Maonekedwe a Microbiwo
Ofufuzawo anachita zingwe 16 za RRNA pogwiritsa ntchito DNA yochokera ku chotupa chofananira ndi maofesi athanzi kuyambira maola 246 (Chithunzi 3a). Kuti akatsimikizire, ofufuzawo amasanthulanso 16s RRNA amasokoneza zitsulo kuchokera ku zitsanzo zowonjezera 42 zomwe sizinafanane ndi kuwunika. Choyamba, ofufuzawo adafanizira kuchuluka kwa maluwa pakati pa zotupa ndi maofesi athanzi. Chowonjezera cha comstridium chinachuluka kwambiri poyerekeza ndi zitsanzo zabwino (Chithunzi 3A-3D). Panalibe kusiyana kwakukulu pamitundu ya alpha (mitundu yosiyanasiyana ya mitundu imodzi) pakati pa chotupa chofufumitsa komanso chathanzi, komanso kuchepetsedwa kwa zotupa zazitali kwambiri.
Kuti mupeze mayanjano oyenera am'mimba pakati pa microbial mapangidwe ndi zotsatira zamankhwala, ofufuzawo akufuna kugwiritsa ntchito zitsulo 16s RRNAQueness cereza zomwe zimapangitsa kuti kupulumuka. Ku AC-ICAM246, ofufuzawo adathamangitsa mtundu wa os Cox omwe amasankhidwa kukhala osankhidwa (omwe amaphatikizidwa ndi zoopsa zosadziwika)
Mu maphunziro awa (ICAM246), kuchuluka kotsika kwa MBR Ofufuzawo adatsimikizira kuti mayanjano otsika kwambiri a MBR .
3
Chithunzi 3. Microbiome mu chotupa komanso ubwenzi ndi ICR ndi wodwala.
Mapeto
Njira yodziwika bwino yophunzirira iyi imathandizira kudziwa bwino komanso kusanthula kwa osagwirizana ndi kusaina kwa chitetezo cha mthupi cha chitetezo cha colobiome ndi chitetezo cha mthupi. Kuchepa kwa TCR ya chotupa chotupa ndi thanzi lapansi kunavumbula kuti kufunikira kwa icr kungakhale chifukwa chotupa chotupa ndi chotupa chotupa.

Posanthula chotupa cha chotupa pogwiritsa ntchito 16s RRNA imasokoneza zitsanzo mu AC-ICAm, gululi lidazindikira siginecha ya microbiome (MBR HORD) ndi phindu lamphamvu. Ngakhale kuti siginechayi idachokera ku chotupa cha chotupa, panali kulumikizana kwamphamvu pakati pa zoopsa za may colorectom ndi chiwopsezo cha MBR, ndikuwonetsa kuti siginecha iyi ikhoza kujambulidwa mumicrobiome kapangidwe ka matenda a mtima. Kuphatikiza pa ICR ndi zigawo za MBR, zinali zotheka kuzindikira ndikutsimikizira wophunzira mankhwala ogwiritsa ntchito biomerker omwe amalosera anthu omwe ali ndi khansa ya m'matumbo. Kusunga kwambiri kwa maphunziro kumapereka gwero kumvetsetsa bwino za khansa ya m'matumbo ndikuthandizira kupeza njira zochizira zamunthu.

Kunena:
Roselands, J., Kuppen, PJK, AHIDED, EI et al. Chotupa cholumikizidwa, chabata ndi microbiiome atlas a khansa ya m'matumbo. Nat Med 29, 1273-1286 (2023).


Post Nthawi: Jun-15-2023
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