Mutant Stem Cells Defy Txoj Cai Kev Txhim Kho

Xav tias koj tab tom ci ncuav mog qab zib, tab sis koj tsis muaj ntsev. Txawm tias muaj cov khoom uas ploj lawm, lub batter tseem zoo li lub ncuav mog qab zib batter, yog li koj lo rau hauv qhov cub thiab hla koj cov ntiv tes, cia siab tias yuav xaus nrog qee yam zoo nkauj ze rau lub ncuav mog qab zib ib txwm. Es tsis txhob, koj rov qab los ib teev tom qab mus nrhiav tau ib tug tag nrho siav steak.

Nws suab zoo li cov lus tso dag, tab sis qhov kev hloov pauv tsis txaus ntseeg no yog qhov tshwm sim tiag tiag rau lub tais ntawm cov kab mob nas thaum cov kws tshawb fawb ntawm Gladstone Institutes tshem tawm tsuas yog ib lub noob qes-stem cell destined los ua lub plawv hlwb dheev zoo li cov precursors rau hlwb hlwb. Cov kws tshawb fawb txoj kev soj ntsuam yog upending qhov lawv xav tias lawv paub txog yuav ua li cas qia hlwb hloov mus rau cov neeg laus thiab tswj lawv tus kheej thaum lawv loj hlob.

Benoit Bruneau, PhD, tus thawj coj ntawm Gladstone Institute of Cardiovascular Disease thiab tus kws sau ntawv laus ntawm txoj kev tshawb fawb tshiab tau hais tias "Qhov no nyuaj rau cov ntsiab lus tseem ceeb txog yuav ua li cas cov hlwb nyob hauv chav kawm thaum lawv pib ua lawv txoj hauv kev los ua lub plawv lossis hlwb hlwb," Xwm.

Tsis Tig Rov Los

Embryonic qia hlwb yog pluripotent-lawv muaj peev xwm sib txawv, los yog hloov, mus rau txhua hom cell hauv lub cev neeg laus tsim tag nrho. Tab sis nws yuav siv sij hawm ntau kauj ruam rau cov qia hlwb kom nce rau cov neeg laus hom. Ntawm lawv txoj kev los ua lub plawv hlwb, piv txwv li, embryonic qia hlwb ua ntej sib txawv rau hauv mesoderm, ib qho ntawm peb cov ntaub so ntswg uas pom nyob rau hauv cov embryos thaum ntxov. Ntxiv mus, cov mesoderm cells tuaj yeem ua rau cov pob txha, cov leeg, cov hlab ntsha, thiab lub plawv dhia.

Nws feem ntau lees paub tias thaum ib lub xov tooj ntawm tes tau pib sib txawv ntawm ib txoj hauv kev no, nws tsis tuaj yeem tig mus xaiv txoj hmoo sib txawv.

“Pretty much every scientist who talks about cell fate uses a picture of the Waddington landscape, which looks a lot like a ski with different ski slopes descending into steep, separated valleys,” says Bruneau, who is also the William H. Younger Chair in Cardiovascular Research at Gladstone and a professor of pediatrics at UC San Francisco (UCSF). “If a cell is in a deep valley, there’s no way for it to jump across to a completely different valley.”

Ib xyoo caum dhau los, Gladstone Senior Investigator Shinya Yamanaka, MD, PhD, nrhiav pom yuav ua li cas reprogram tag nrho cov neeg laus sib txawv rau hauv induced pluripotent qia hlwb. Thaum qhov no tsis ua rau lub hlwb muaj peev xwm dhia ntawm hav, nws tau ua zoo li lub caij ski nqa rov qab mus rau sab saum toj ntawm cov toj roob hauv pes sib txawv.

Txij thaum ntawd los, lwm cov kws tshawb fawb tau tshawb pom tias nrog cov tshuaj cues zoo, qee lub hlwb tuaj yeem hloov mus rau hauv cov kev sib raug zoo sib xws los ntawm cov txheej txheem hu ua "direct reprogramming"-zoo li txoj kev luv los ntawm cov ntoo ntawm cov neeg nyob sib ze. Tab sis tsis muaj ib qho ntawm cov xwm txheej no tuaj yeem ua rau lub hlwb dhia nrawm ntawm txoj kev sib txawv sib txawv. Tshwj xeeb, mesoderm hlwb tsis tuaj yeem dhau los ua qhov ua ntej ntawm hom nyob deb xws li hlwb hlwb lossis lub plab hnyuv.

Txawm li cas los xij, hauv txoj kev tshawb fawb tshiab, Bruneau thiab nws cov npoj yaig qhia tias, ua rau lawv xav tsis thoob, lub plawv cell precursors muaj peev xwm hloov tau ncaj qha mus rau hauv lub hlwb precursors - yog tias cov protein hu ua Brahma ploj lawm.

Ib qho kev soj ntsuam ceeb

Cov kws tshawb fawb tau kawm txog lub luag haujlwm ntawm cov protein Brahma hauv kev sib txawv ntawm lub plawv hlwb, vim tias lawv tau tshawb pom xyoo 2019 tias nws ua haujlwm ua ke nrog lwm cov molecules cuam tshuam nrog kev tsim lub plawv.

Nyob rau hauv ib lub tais ntawm nas embryonic qia hlwb, lawv siv CRISPR genome-editing le caag los tua cov noob Brm (ib qho uas tsim cov protein Brahma). Thiab lawv pom tias cov hlwb tsis sib txawv rau hauv lub plawv cell precursors.

“Tom qab 10 hnub ntawm kev sib txawv, cov hlwb ib txwm ua kom nrawm nrawm; lawv yog cov hlwb kom meej meej, ”hais tias Swetansu Hota, PhD, thawj tus sau ntawm txoj kev tshawb no thiab ib tug neeg ua haujlwm kws tshawb fawb hauv Bruneau Lab. "Tab sis tsis muaj Brahma, tsuas muaj ib pawg ntawm inert hlwb xwb. Tsis muaj kev ntaus txhua. "

Tom qab kev soj ntsuam ntxiv, Bruneau pab neeg pom tau tias yog vim li cas lub hlwb tsis raug ntaus yog vim tias tshem Brahma tsis tsuas yog tua cov noob uas xav tau rau lub plawv hlwb, tab sis kuj tseem siv cov noob uas xav tau hauv hlwb hlwb. Lub plawv precursor hlwb tam sim no lub hlwb precursor hlwb.

Cov kws tshawb fawb tom qab ntawd ua raws txhua kauj ruam ntawm kev sib txawv, thiab nrhiav pom tsis tau tias cov hlwb no tsis tau rov qab los rau lub xeev pluripotent. Hloov chaw, cov hlwb coj qhov kev dhia loj dua ntawm txoj kev qia cell dua li tau pom ua ntej.

"Qhov peb pom yog tias lub xov tooj ntawm tes hauv ib lub hav ntawm Waddington toj roob hauv pes, nrog rau cov xwm txheej zoo, tuaj yeem dhia mus rau hauv ib lub hav sib txawv yam tsis tau nqa lub nqa rov qab mus rau qhov ua siab tshaj," Bruneau hais.

Zaj Lus Qhia Txog Kab Mob

Txawm hais tias ib puag ncig ntawm cov hlwb hauv chav kuaj thiab hauv ib lub embryo tag nrho txawv heev, cov kws tshawb fawb cov kev soj ntsuam tuav cov lus qhia txog kev noj qab haus huv ntawm tes thiab kab mob. Kev hloov pauv hauv cov noob Brm tau cuam tshuam nrog cov kab mob hauv lub plawv thiab nrog cov tsos mob uas cuam tshuam nrog lub hlwb ua haujlwm. Cov noob kuj tseem koom nrog ntau yam qog nqaij hlav.

"Yog tias tshem Brahma tuaj yeem hloov mesoderm hlwb (xws li lub plawv cell precursors) mus rau hauv ectoderm cells (xws li hlwb hlwb precursors) hauv cov tais diav, tej zaum kev hloov pauv hauv cov noob Brm yog dab tsi muab qee lub hlwb muaj peev xwm los hloov kho lawv cov caj ces, " hais tias Bruneau.

Cov kev tshawb pom kuj tseem ceeb ntawm qib kev tshawb fawb, nws hais ntxiv, vim tias lawv tuaj yeem tso lub teeb pom kev yuav ua li cas cov hlwb yuav hloov lawv tus cwj pwm hauv cov kab mob, xws li lub plawv tsis ua hauj lwm, thiab tsim kho cov kev kho mob, los ntawm kev tsim cov hlwb tshiab piv txwv.

Bruneau hais tias "Peb txoj kev tshawb fawb tseem qhia peb tias txoj kev sib txawv yog qhov sib txawv thiab tsis yooj yim dua li qhov peb xav," "Kev paub zoo dua ntawm txoj hauv kev ntawm kev sib txawv kuj tuaj yeem pab peb nkag siab lub siab lub hauv paus - thiab lwm yam - tsis xws luag, uas tshwm sim hauv ib feem los ntawm kev sib txawv."

Print Friendly, PDF & Email

Xov Xwm Lwm Yam