Tib-Cell Transcriptomics nthuav tawm Kev cuam tshuam rau lub raum lim Cell-Cell Interactions tom qab ntxov thiab xaiv Podocyte raug mob Ⅲ

Kev sib tham

Podocyte tsis ua haujlwmthiabpoobyog covua rau muaj ntau yam mob raum. Txoj kev tshawb no tau siv scRNAseq los txheeb xyuas cov kev sib txuas lus sib txuas lus thiab xov tooj ntawm tes sib tham hauvglomerular qhov chawTsis ntev tom qab induction ntawm xaiv podocyte raug mob. Txoj kev tshawb no coj kom zoo dua ntawm amouse qauv ntawm iCTCFpod / ntawm 1 lub lis piam tom qab induction los tsim ib tug cell daim ntawv qhia ntawm lub raum lim nyob rau hauv lub ntxov theem ntawmkev raug mob podocyte. Qhov kev tshawb fawb dav dav ntawm cov hlwb glomerular, thawj zaug los ntsuas qhov cuam tshuam ntawm ib qho tshwj xeeb thiab kev xaiv caj ces perturbation, tau qhia plaub qhov kev nkag siab tseem ceeb ntawmlub raum limhauv kev noj qab haus huv thiab kab mob.

NEW HERBS RAUPODOCYTE DYSFUNCTION

Ua ntej, scRNAseq tau ua tiav tom qab 1 lub lis piam ntawm kev kho doxycycline kom ntxias CTCF tshem tawm hauv iCTCFpod / tsiaj txhawm rau txheeb xyuas qhov kev hloov pauv ntxov tshaj plaws uas tshwm sim tom qab raug mob podocyte. Txawm hais tias podocyte quantifica tion los ntawm cov duab tsom xam pom qhov sib txawv ntawm cov naj npawb ntawm cov podocytes hauv WT thiab iCTCFpod / glomeruli tom qab 2 lub lis piam ntawm kev kho doxycycline, 13 qhov txo qis ntawm podocytes hauv iCTCFpod / glomeruli tau pom txawm tias tom qab 1 lub lis piam ntawm doxycycline induction. Qhov kev tshawb pom no qhia tias kev cuam tshuam ntawm cov kev pabcuam transcriptional tseem ceeb rau podocyte ciaj sia ua ntej histologically detectable podo cyte raug mob thiab poob thiab qhia txog lub zog ntawm scRNAseq nyob rau hauv cov kev hloov pauv hloov maj mam uas tuaj yeem plam los ntawm histo logic tsom xam. Nyob rau theem siab, qhov kev tshawb pom no qhia tias kev siv zog los tsim kho podocyte-tiv thaiv kev kho mob yuav tsum tsom rau kev tiv thaiv kev raug mob podocyte kom ntxov li sai tau thaum muaj tus kab mob.

Thib ob, kev txhawb nqa rau glomeruli los ntawm tag nrho ob lub raum siv txoj kev sieving tau siv los ua kom cov txheej txheem ntawm cov kab mob glomerular cais tawm uas tau zoo, suav nrog cov neeg tsis tshua muaj PECs uas tsis tau raug ntes hauv scRNAseq cov kev tshawb fawb yav dhau los.9,22,51 Ntxiv rau. , txhua hom cell loj ntawm lub raum raug txheeb xyuas. Qhov kev txheeb xyuas no muab lub sijhawm rau cov kev tshawb fawb yav tom ntej los ntsuas cov kev hloov pauv hloov pauv uas tau tsav los ntawm kev raug mob podocyte nyob rau hauv tag nrho lub raum, uas yuav ua kom nkag siab tob txog cov xwm txheej ntawm lub raum thoob plaws cov xwm txheej uas ua rau kev loj hlob ntawm CKD.

Thib peb, cov ntaub ntawv qhia tias iCTCFpod / nas qauv recapitulates ntau yam ntawm tib neeg cov kab mob nyob rau hauv lub transcriptional theem, nrog rau kev qhia txawv ntawm cov noob tseem ceeb rau podocyte adherence rau GBM thiab autocrine prosurvival ligands. Vim tias kev ua raws li podo cytes rau GBM yog qhov tseem ceeb rau lawv txoj haujlwm, kev tswj hwm ntawm Col4a5 thiab lwm cov noob hauv cell adhesion cov kev pab cuam txhawb nqa tus qauv uas podocytes teb rau qhov pib raug mob los ntawm kev ua raws li GBM. Tib neeg kev hloov pauv hauv podocyte focal adhesion noob, suav nrog cov noob ntawm actin cytoskeleton, hom IV collagen, thiab integrins, txhua tus tau cuam tshuam hauv FSGS thiab / lossis nephrotic syndrome.52,53 Tsis tas li ntawd, ligand-receptor tsom xam tau qhia tias cov teeb liab molecules cuam tshuam rau tib neeg DKD yog kuj cuam tshuam rau hauv CTCF nas qauv (piv txwv li, BMP4 thiab Col4a1).41,42,44 Peb kuj tau soj ntsuam qhov dysregulation ntawm ob qho tseem ceeb autocrine prosurvival ligands, Vegfa thiab Pdgfb, uas nws lub luag hauj lwm tau tsim zoo hauv vitro thiab hauv vivo, thiab kev hloov pauv. Hauv lawv cov kev qhia thiab / lossis kev ua haujlwm tau cuam tshuam nrog tib neeg lub raum kab mob, xws li thrombotic microangiopathies thiab DKD.54 Tshwj xeeb tshaj yog, kev kho tshuaj tiv thaiv VEGF, kev kho mob qog noj ntshav, ua rau lub raum throm botic microangiopathy, 55 thiab Pdgfb qhia tau nce hauv tib neeg. Lub raum biopsy cov qauv ntawm cov neeg mob nrog DKD thiab mesangial proliferative glomerulonephritis.56e58 Ua ke, cov ntaub ntawv no txhawb kev xav tias tus qauv iCTCFpod / nas tuaj yeem muab cov lus qhia ncaj ncees ntawm kev hloov pauv glomerular thaum ntxov nrog rau ntau yam kab mob hauv tib neeg lub raum.

Kev lees paub

Peb ua tsaug rau Aviv Regev, Orit Rosenblatt-Rosen, thiab cov tswv cuab ntawm pab pawg Regev rau cov lus qhia txuas ntxiv ntawm ib lub xov tooj ntawm tes thev naus laus zis thiab kev suav nrog, thiab Broad GP platform rau cov kev pabcuam sequencing.

Sau Kev Pab Txhawb

ARC, JM, thiab AG tsim cov kev sim; ARC tau ua kev sim tsiaj, pab los ntawm YZ thiab MSMARC ua kev txheeb xyuas ntawm ib leeg-cell RNA sequencing cov ntaub ntawv; LN tsim thiab ua raws 10 lub tsev qiv ntawv; JM tau ua HCR kev sim; HC tau ua HCR suav kev txheeb xyuas kom muaj nuj nqis; AG coj qhov project; thiab ARC thiab AG tau sau cov ntawv sau. Txhua tus kws sau ntawv nyeem, tawm tswv yim, thiab pom zoo cov ntawv sau.

Cov ntaub ntawv

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