Dhx15 regulates zebrafish definitive hematopoiesis through the unfolded protein response pathway.
Dhx15 regulates zebrafish definitive hematopoiesis through the unfolded protein response pathway.
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Dhx15通过未折叠蛋白反应途径调节斑马鱼的定性造血
DOI：
10.1111/cas.15002
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发表时间：
2021-09
期刊：
影响因子：
5.7
通讯作者：
Wang S
中科院分区：
文献类型：
--
作者：
Cai Y;Wang J;Jin D;Liu Q;Chen X;Pan L;Li Y;Wang X;Qian F;Wang J;Zhong TP;Wang S
Gene alterations are recognized as important events in acute myeloid leukemia (AML) progression. Studies on hematopoiesis of altered genes contribute to a better understanding on their roles in AML progression. Our previous work reported a DEAH box helicase 15 (DHX15) R222G mutation in AML patients, and we showed DHX15 overexpression is associated with poor prognosis in AML patients. In this work, we further study the role of dhx15 in zebrafish developmental hematopoiesis by generating dhx15−/− zebrafish using transcription activator‐like effector nuclease technology. Whole‐mount in situ hybridization (WISH) analysis showed hematopoietic stem/progenitor cells were dramatically perturbed when dhx15 was deleted. Immunofluorescence staining indicated inhibited hematopoietic stem/progenitor cell (HSPC) proliferation instead of accelerated apoptosis were detected in dhx15−/− zebrafish. Furthermore, our data showed that HSPC defect is mediated through the unfolded protein response (UPR) pathway. DHX15 R222G mutation, a recurrent mutation identified in AML patients, displayed a compromised function in restoring HSPC failure in dhx15−/−; Tg (hsp: DHX15 R222G) zebrafish. Collectively, this work revealed a vital role of dhx15 in the maintenance of definitive hematopoiesis in zebrafish through the unfolded protein respone pathway. The study of DHX15 and DHX15 R222G mutation could hold clinical significance for evaluating prognosis of AML patients with aberrant DHX15 expression.
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影响因子：
30.8
作者：
Faber ZJ;Chen X;Gedman AL;Boggs K;Cheng J;Ma J;Radtke I;Chao JR;Walsh MP;Song G;Andersson AK;Dang J;Dong L;Liu Y;Huether R;Cai Z;Mulder H;Wu G;Edmonson M;Rusch M;Qu C;Li Y;Vadodaria B;Wang J;Hedlund E;Cao X;Yergeau D;Nakitandwe J;Pounds SB;Shurtleff S;Fulton RS;Fulton LL;Easton J;Parganas E;Pui CH;Rubnitz JE;Ding L;Mardis ER;Wilson RK;Gruber TA;Mullighan CG;Schlenk RF;Paschka P;Döhner K;Döhner H;Bullinger L;Zhang J;Klco JM;Downing JR
通讯作者：
Downing JR
影响因子：
--
作者：
Nik S;Weinreb JT;Bowman TV
通讯作者：
Bowman TV
影响因子：
3.5
作者：
McElderry, John;Carrington, Blake;Sood, Raman
通讯作者：
Sood, Raman
DHX15 与急性髓系白血病 (AML) 的不良预后相关，并通过 NF-kB 信号通路调节细胞凋亡。
影响因子：
--
作者：
Pan L;Li Y;Zhang HY;Zheng Y;Liu XL;Hu Z;Wang Y;Wang J;Cai YH;Liu Q;Chen WL;Guo Y;Huang YM;Qian F;Jin L;Wang J;Wang SY
通讯作者：
Wang SY
影响因子：
11.2
作者：
Farrar JE;Schuback HL;Ries RE;Wai D;Hampton OA;Trevino LR;Alonzo TA;Guidry Auvil JM;Davidsen TM;Gesuwan P;Hermida L;Muzny DM;Dewal N;Rustagi N;Lewis LR;Gamis AS;Wheeler DA;Smith MA;Gerhard DS;Meshinchi S
通讯作者：
Meshinchi S