Iiseli ze-Mutant Stem ziyayityeshela iMithetho yoPhuhliso

Khawucinge ukuba ubhaka ikeyiki, kodwa uphelelwe yityuwa. Nangona isithako esilahlekileyo, i-batter isabonakala ngathi i-cake batter, ngoko uyinamathele ehovini kwaye uwele iminwe yakho, ulindele ukugqiba into esondeleyo kwikhekhe eliqhelekileyo. Kunoko, ubuya emva kweyure ukuze ufumane i-steak ephekwe ngokupheleleyo.

Kuvakala ngathi liqhula elisebenzayo, kodwa olu hlobo lwenguqu eyothusayo yinto eyenzeka ngokwenene kwisitya seeseli zempuku xa izazinzulu zaseGladstone Institutes zasusa umfuzo nje omnye—iiseli zestem ezimiselwe ukuba zibe ziiseli zentliziyo ngequbuliso zifane nezandulela kwiiseli zengqondo. Ukujongwa kwethuba lezazinzulu kuphakamisa oko bebecinga ukuba bayayazi malunga nendlela iiseli eziguqukayo zibe ziiseli zabantu abadala kwaye zigcine ubuni bazo njengoko zikhula.

"Oku kucela umngeni kwiingcamango ezisisiseko malunga nendlela iiseli ezihlala ngayo kwikhosi xa ziqala indlela yazo yokuba yintliziyo okanye iiseli zengqondo," utshilo uBenoit Bruneau, PhD, umlawuli weGladstone Institute of Cardiovascular Disease kunye nombhali ophezulu wophononongo olutsha olupapashwe. Indalo.

Akukho kubuya mva

Iiseli ze-Embryonic stem zi-pluripotent-zinamandla okuhlula, okanye ukuguqula, kwiintlobo zonke zeeseli kumzimba omdala owenziwe ngokupheleleyo. Kodwa kuthatha amanyathelo amaninzi kwiiseli ze-stem ukuba zivelise iintlobo zeeseli zabantu abadala. Kwindlela yabo eya ekubeni ziiseli zentliziyo, umzekelo, iiseli ze-embryonic stem ziqala ukwahlula kwi-mesoderm, esinye sezihlunu ezintathu zamandulo ezifunyenwe kwiimbumba zokuqala. Ukuqhubela phambili kwindlela, iiseli ze-mesoderm zihamba ukuze zenze amathambo, izihlunu, imithambo yegazi kunye neeseli zentliziyo.

Yamkelwa ngokubanzi ukuba xa iseli sele iqalisile ukwahlula enye yale ndlela, ayinakujika ikhethe elinye ikamva.

UBruneau, okwanguSihlalo kaWilliam H. Omncinane uthi: “Kakade sonke isazinzulu esithetha ngekamva leseli sisebenzisa umfanekiso wendawo yaseWaddington, ekhangeleka ngathi yindawo yokutyibiliza etyibilizini enamathambeka ahlukeneyo okutyibilika ezantsi emathambekeni ahlukeneyo entlambo. kuPhando lweCardiovascular eGladstone kunye noprofesa wezifo zabantwana kwi-UC San Francisco (UCSF). Ukuba iseli ikwintlambo enzulu, akukho ndlela yakutsibela kwintlambo eyahluke ngokupheleleyo.

Kwiminyaka elishumi edlulileyo, umphandi oMkhulu weGladstone uShinya Yamanaka, MD, PhD, wafumanisa indlela yokuhlaziya iiseli zabantu abadala ezahlulwe ngokupheleleyo kwiiseli ze-pluripotent stem. Ngelixa oku kungakhange kunikeze iiseli amandla okutsiba phakathi kweentlambo, zenze njengokuphakanyiselwa kwe-ski umva ukuya phezulu kwindawo yokwahlulahlula.

Ukusukela ngoko, abanye abaphandi baye bafumanisa ukuba ngeekhemikhali ezichanekileyo, ezinye iiseli zinokuguqulwa zibe ziintlobo ezinxulumene ngokusondeleyo ngenkqubo ebizwa ngokuba yi “direct reprogramming”—njengendlela emfutshane etyholweni phakathi kweendlela ezikufuphi zokutyibiliza. Kodwa akukho nanye kwezi meko apho iiseli zinokutsibela ngokuzenzekelayo phakathi kweendlela ezahlukeneyo zokwahlula. Ngokukodwa, iiseli ze-mesoderm azinakuba ngabaphambili beentlobo ezikude njengeeseli zengqondo okanye iiseli zamathumbu.

Ukanti, kolu hlolisiso lutsha, uBruneau noogxa bakhe babonisa ukuba, into eyothusayo kukuba, iiseli zentliziyo ziyakwazi ukuguquka zibe ziiseli zengqondo—ukuba iproteni ebizwa ngokuba yiBrahma ayikho.

Umbono Omangalisayo

Abaphandi babefunda indima yeprotheyini yeBrahma ekwahlulweni kweeseli zentliziyo, kuba bafumanisa ngo-2019 ukuba isebenza kunye nezinye iimolekyuli ezinxulumene nokwakheka kwentliziyo.

Kwisitya seeseli ze-embryonic stem, basebenzise iindlela ze-CRISPR zokuhlela i-genome ukucima i-gene Brm (leyo ivelisa i-protein Brahma). Kwaye baqaphela ukuba iiseli azisekho ukwahlula kwii-precursors zeseli zentliziyo eziqhelekileyo.

“Emva kweentsuku ezili-10 zokwahlukana, iiseli eziqhelekileyo zibetha ngesingqi; ziiseli zentliziyo ngokucacileyo,” utshilo uSwetansu Hota, PhD, umbhali wokuqala wophononongo kunye nesazinzulu sabasebenzi kwiLebhu yaseBruneau. Kodwa ngaphandle kweBrahma, kwakukho inkitha yeeseli ezingasebenziyo. Akukho kubethwa kwaphela.”

Emva kohlalutyo olongezelelweyo, iqela likaBruneau laqonda isizathu sokuba iiseli zingabetheli kungenxa yokuba ukususa i-Brahma akuzange kucinywe kuphela izakhi zofuzo ezifunekayo kwiiseli zentliziyo, kodwa kunye neegesi ezisebenzayo ezifunekayo kwiiseli zengqondo. Iiseli ze-precursor yentliziyo ngoku yayiziiseli ezandulela ingqondo.

Abaphandi ke balandela inyathelo ngalinye lokwahlula, kwaye bafumanisa ngokungalindelekanga ukuba ezi seli azizange zibuyele kwimeko ye-pluripotent. Endaweni yoko, iiseli zathatha umtsi omkhulu ngakumbi phakathi kweendlela zeeseli ze-stem kunokuba zazikhe zabonwa ngaphambili.

UBruneau uthi: “Esakubonayo kukuba isisele esikwintlambo ethile ekwilizwe laseWaddington, enemeko efanelekileyo, sinokutsibela kwintlambo eyahlukileyo ngaphandle kokuba siqale siphakamisele phezulu sibuyela encotsheni.

Izifundo ngeZifo

Ngelixa indawo engqongileyo yeeseli kwisitya selebhu kunye nakwi-embryo yonke yahluke kakhulu, uqwalaselo lwabaphandi lubambe izifundo malunga nempilo yeeseli kunye nezifo. Ukuguqulwa kwe-gene ye-Brm kuye kwadibaniswa nesifo senhliziyo sokuzalwa kunye ne-syndromes ebandakanya ukusebenza kwengqondo. Ufuzo lukwabandakanyeka kwimihlaza emininzi.

"Ukuba ukususa iBrahma kunokuguqula iiseli ze-mesoderm (njengeeseli zentliziyo) zibe ziiseli ze-ectoderm (njengezandulela zeeseli zengqondo) esityeni, mhlawumbi uguqulo lwemfuza ye-Brm luthi lunike ezinye iiseli zomhlaza ukuba zikwazi ukuguqula kakhulu inkqubo yazo yemfuza, " utshilo uBruneau.

Iziphumo nazo zibalulekile kwinqanaba lophando olusisiseko, uyongezelela, njengoko banokukhanyisa indlela iiseli ezinokuthi zitshintshe ngayo iimpawu zabo kwimimiselo yezifo, ezifana nokungaphumeleli kwentliziyo, kunye nokuphuhlisa unyango oluhlaziyiweyo, ngokubangela iiseli ezintsha zentliziyo umzekelo.

“Uphononongo lwethu lukwasixelela ukuba iindlela zokwahlula zintsonkothile kwaye zibuthathaka kunokuba besicinga,” utshilo uBruneau. "Ulwazi olungcono lweendlela zokwahlula lunokusinceda ukuba siqonde intliziyo yokuzalwa-kunye nezinye-iziphene, ezithi zivele ngokuyinxenye ngenxa yokwahlukana okungalunganga."