2024騫?鏈?9鏃ワ紝浜戝崡澶у闄堝ぇ鍗庢暀鎺堝洟闃熷強鍏跺悎浣滆€呭湪Cell Press鏃椾笅鐭ュ悕瀛︽湳鏈熷垔Cell Reports鍦ㄧ嚎鍙戣〃浜嗛涓衡€淭he TET-Sall4-BMP regulatory axis controls craniofacial cartilage development鈥濈殑鐮旂┒璁烘枃錛屽彂鐜癟ET瀹舵棌铔嬬櫧錛圱ET2銆乀ET3錛夊拰杞綍鍥犲瓙Sall4鍙戠敓鍏卞悓鐩稿垎紱誨艦鎴愬嚌鑱氫綋錛岃皟鎺MP淇″彿閫氳礬媧繪€э紝浠庤€屽獎鍝嶅鑳氬眰闂村厖璐ㄧ粏鑳炲悜杞緇嗚優鐨勫垎鍖栥€俆ET-Sall4-BMP璋冩帶杞村湪鑳氳儙鍙戣偛鐨勯闈㈣蔣楠ㄥ彂鐢熶腑鍙戞尌鍏抽敭鍔熻兘銆?/p>
棰呴潰鐭皬鐥囷紙Craniofacial Microsomia, CFM錛夋槸涓€縐嶅父瑙佺殑鍏堝ぉ鎬у緋葷粺鍙戣偛鐣稿艦錛屽彂鐥呯巼楂樿揪1/5000浠ヤ笂錛屾偅鑰呭琛ㄧ幇涓鴻€抽儴鍜屼笅棰岄鐨勫彂鑲插紓甯搞€傜洰鍓嶏紝璇ョ梾鐨勪復搴婅〃鍨嬪鏉傘€佸彂鐥呮満鍒跺皻涓嶆槑紜€傝繎騫存潵錛屾湁鐥呬緥鎶ラ亾縐版惡甯︾壒瀹歍en-eleven translocation錛圱ET錛夊熀鍥犲彉寮傚瀷鐨勬偅鑰呰〃鐜板嚭鍏稿瀷鐨勯闈㈢暩褰㈢棁鐘躲€侱NA鍙屽姞姘ч叾TET瀹舵棌铔嬬櫧浣滀負閲嶈鐨勮〃瑙傞仐浼犺皟鎺у洜瀛愶紝鍙粙瀵?-鐢插熀鑳炲槯鍟訛紙5-mC錛夎漿鍖栦負5-緹熺敳鍩鴻優鍢у暥錛?-hmC錛夈€傚叧浜嶵ET铔嬬櫧鏄惁鍙備笌璋冩帶棰呴潰鍙戣偛榪涜€屼笌CFM鍙戠梾鐩稿叧鑱斿垯浠嶇劧鏈煡銆?/p>
涓轟簡鎻ず榪欎竴闂錛岀爺絀朵漢鍛樹互鏂戦┈楸間負鍔ㄧ墿妯″瀷錛屽垎鍒瀯寤轟簡TET瀹舵棌鎴愬憳TET1/TET2/TET3鐨勫崟紿佸彉浣撲互鍙?縐嶅弻綰悎紿佸彉浣撱€傜粨鍚堢獊鍙樹綋浠ュ強morpholino浠嬪鐨勫熀鍥犳暡闄嶅疄楠岃繘琛岃〃鍨嬪垎鏋愶紝鍙戠幇TET2/3鍚屾椂緙哄け浼氬鑷存槑鏄劇殑涓嬮杞鍙戣偛鐣稿艦銆傚熀浜庢櫘閫氳漿褰曠粍嫻嬪簭浠ュ強鍗曠粏鑳炶漿褰曠粍嫻嬪簭鏁版嵁鐨勫垎鏋愯〃鏄庯紝TET2/3緙哄け涓嶄粎寮曡搗浜嗗墽鐑堢殑鍩哄洜琛ㄨ揪鍙樺寲錛屾洿涓ラ噸褰卞搷浜嗘枒椹奔鑳氳儙涓殑緇嗚優璋辯郴鍙戣偛銆備互鏄捐憲鍙楀共鎵扮殑杞鍙戠敓榪囩▼涓轟緥錛氬鑳氬眰闂村厖璐ㄧ粏鑳烇紙Ectomesenchymal cells錛孍MCs錛夋潵婧愪簬紲炵粡宓寸粏鑳烇紝閮ㄥ垎澶栬儦灞傞棿鍏呰川緇嗚優灝嗚繘涓€姝ュ垎鍖栦負杞緇嗚優錛涙嫙鏃跺簭鍒嗘瀽鏄劇ずTET2/3緙哄け瀵艱嚧榪欎竴榪囩▼鍙楀埌闃婚亸鏃犳硶姝ｅ父榪涜銆侲MC鐨勮氨緋誨彂鑲插彈鍒板寘鎷琖nt錛孎GF錛孊MP絳夊湪鍐呯殑澶氫釜淇″彿閫氳礬璋冩帶錛岃€屽綋TET2/3緙哄け鍚庯紝BMP閫氳礬鐩稿叧緇勫垎鐨勮〃杈懼彈褰卞搷鏇翠負鏄捐憲銆傞仐浼犲璇佹嵁琛ㄦ槑錛岃繃琛ㄨ揪Bmp4鎴朣mad1CA鍧囧彲鏄庢樉鍥炲鍥燭ET2/3緙哄け瀵艱嚧鐨勪笅棰岃蔣楠ㄧ暩褰€備互涓婄粨鏋滆瘉鏄嶵ET2/3閫氳繃褰卞搷BMP淇″彿閫氳礬媧繪€ф潵鎺у埗杞緇嗚優鍒嗗寲銆?/p>
鎺ヤ笅鏉ワ紝鐮旂┒鑰呭埄鐢╤MeDIP-seq錛孊S/ox-BS-seq絳夋妧鏈瀯寤轟簡鏂戦┈楸艱儦鑳庣簿緇嗙殑鍏ㄥ熀鍥犵粍5hmC鍒嗗竷鍥捐氨銆傜浉杈冧簬閲庣敓鍨嬫牱鏈紝褰揟ET2/3鏁查檷鍚庡鑷碆mp4鍚姩瀛愮壒瀹氬尯鍩熺殑5hmC peak娑堝け銆傞€氳繃鍒嗘瀽搴忓垪鐨刴otif鐗瑰緛鐒跺悗榪涜DNA鎺㈤拡pull-down闈惰泲鐧借川璋遍壌瀹氭妧鏈紝鎺ㄦ祴杞綍鍥犲瓙Sall4鍙兘鏄皟鎺mp4琛ㄨ揪鐨勫叧閿泲鐧姐€傚熀浜庡師浣嶆潅浜や互鍙婅〃鍨嬪垎鏋愮殑璇佹嵁鏄劇ずSall4琛ㄨ揪妯″紡涓嶣mp4楂樺害綾諱技錛孲all4緙哄け浼氬鑷翠笅棰岃蔣楠ㄧ暩褰互鍙夿mp4琛ㄨ揪鏄捐憲涓嬭皟錛岃繃琛ㄨ揪Bmp4鍒欏彲浠ユ槑鏄懼洖澶嶅洜Sall4緙哄け瀵艱嚧鐨勮〃鍨嬨€傜敱姝ゆ帹鏂璖all4涔熷彲鑳介€氳繃Bmp4鍙備笌璋冩帶涓嬮杞鍙戣偛銆傛澶栵紝Sall4鍋忓ソ鎬х粨鍚?mC/5hmC淇グ鐨凞NA鍒嗗瓙錛屾剰鍛崇潃Sall4涓嶵ET浠嬪鐨?mC/5hmC杞寲榪囩▼瀛樺湪鍏寵仈銆?/p>
涓洪槓鏄庢洿娣卞叆鐨勫垎瀛愭満鍒訛紝鐮旂┒鑰呴€氳繃ddFP緋葷粺緇撳悎媧葷粏鑳炴樉寰垚鍍忓疄楠岃瀵熷埌Sall4涓嶄粎鑷韓鍙互鍑濊仛褰㈡垚灝忛綺掞紝褰揇NA鍒嗗瓙瀛樺湪鏃訛紝Sall4榪樿兘蹇€熷彂鐢熺浉鍙樺艦鎴愭洿澶х殑棰楃矑銆傛湁鎰忔€濈殑鏄紝TET2鎴朤ET3鑷韓闅句互鑱氶泦錛岃€孲all4鐨勫瓨鍦ㄤ細鍒嗗埆淇冭繘Sall4-TET2鍜孲all4-TET3鍙戠敓鍏卞悓鐩稿垎紱誨艦鎴愬ぇ鐨勫嚌鑱氫綋錛屽茍涓擲all4铔嬬櫧鐨刏FC1緇撴瀯鍩熷鍏卞悓鐩稿垎紱葷殑鍙戠敓璧峰叧閿綔鐢ㄣ€傞€氳繃榪欎竴榪囩▼錛孴ET-Sall4鍏卞悓璋冩帶Bmp4琛ㄨ揪銆傜患涓婏紝璇ョ爺絀舵彮紺轟簡TET-Sall4-BMP璋冩帶杞存帶鍒墮闈㈣蔣楠ㄥ彂鑲茬殑璇︾粏鍒嗗瓙鏈哄埗錛屽浜庣悊瑙FM鐨勫彂鐥呮満鍒跺拰璇婃柇絳涙煡鍏鋒湁閲嶈鎰忎箟銆?/p>
浜戝崡澶у鍗氬＋鐮旂┒鐢熺帇浼熷垰銆佹潹濞溿€佺帇浜寒涓鴻鏂囩殑騫跺垪絎竴浣滆€咃紝浜戝崡澶у闄堝ぇ鍗庢暀鎺堛€佺珷鏂囦俊鍓暀鎺堬紝鍗庡崡鐞嗗伐澶у鐜嬪己鏁欐巿銆佹槅鏄庡尰縐戝ぇ瀛﹂檮灞炲彛鑵斿尰闄㈢帇鍗孩鏁欐巿涓鴻鏂囩殑鍏卞悓閫氳浣滆€呫€傛湰欏圭洰寰楀埌鍥藉鑷劧縐戝鍩洪噾鍩虹縐戝涓績欏圭洰鐨勮祫鍔┿€?/p>
璁烘枃閾炬帴錛?/p>
https://www.cell.com/cell-reports/fulltext/S2211-1247(24)00201-8
