A single copy of large tumor suppressor 1 or large tumor suppressor 2 is sufficient for normal hematopoiesis

作     者：Zhi-Gang Li Xue-Mei Fu Cheng-Yan Chai Fang-Fang Sun Fei-Fei Xiao Yong-Xiu Huang Kai Yao Jie-Ping Chen Yu Hou Li Zhi-Gang;Fu Xue-Mei;Chai Cheng-Yan;Sun Fang-Fang;Xiao Fei-Fei;Huang Yong-Xiu;Yao Kai;Chen Jie-Ping;Hou Yu

作者机构：Department of HematologySouthwest HospitalThird Military Medical University(Army Medical University)Chongqing 430008China Medical Research CenterSouthwest HospitalThird Military Medical University(Army Medical University)Chongqing 430008China College of Life Sciences and HealthWuhan University of Science and TechnologyWuhanHubei 430081China 

出 版 物：《Chinese Medical Journal》 (中华医学杂志（英文版）)

年 卷 期：2020年第133卷第16期

页      面：1943-1951页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：Supported by grants from the National Key R&D Program of China(No.2017YFA0106700) National Natural Science Foundation of China(No.81670096) Natural Science Foundation of Chongqing(No.CSTC2016JCYJA0354) Army Major Scientific Research Projects(No.AWS17J007) Military Medical Innovation Program(No.SWH2018QNKJ-09,No.SWH2018LJ-07,and No.SWH2016ZDCX1010) the Hubei Natural Science Foundation(No.2018CFB434) 

主　　题：Hippo pathway Hematopoietic stem cells Stem cell self-renewal 

摘      要：Background:Hematopoietic stem cells(HSCs)have the ability to differentiate into all subsets of blood cells and *** tumor suppressor 1(LATS1)and large tumor suppressor 2(LATS2)kinases are essential for cell cycle regulation,organism fitness,genome integrity,and cancer ***,we investigated whether Lats1 and Lats2 are critical for the maintenance of the selfrenewal and quiescence capacities of HSCs in ***:Quantitative reverse transcription-polymerase chain reaction was used to determine the expression levels of Lats1 and Lats2 in subsets of progenitor cells and mature bone marrow cells.A clustered regularly interspaced short palindromic repeats system was used to generate Lats1 or Lats2 knockout *** blood cell counts were used to compare the absolute number of white blood cells,lymphocytes,monocytes,neutrophils,and platelets between Lats1 or Lats2 heterozygotes and *** cytometry was used to assess the size of hematopoietic progenitor cells(HPCs)and HSC pools in Lats1 or Lats2 heterozygotes and *** comparison between the two groups was analyzed using Student’s t ***:Lats1 and Lats2 were widely expressed in hematopoietic cells with higher expression levels in primitive hematopoietic cells than in mature ***1 or Lats2 knockout mice were generated,with the homozygotes showing embryonic *** size of the HPC and HSC pools in Lats1(HPC:wild-type[WT]***,220,426.77±54,384.796 vs.221,149.4±42,688.29,P=0.988;HSC:WT ***,2498.932±347.856 vs.3249.763±370.412,P=0.105)or Lats2(HPC:WT ***,425,540.52±99,721.86 vs.467,127.8±89,574.48,P=0.527;HSC:WT ***,4760.545±1518.01 vs.5327.437±873.297,P=0.502)heterozygotes were not ***,the depletion of Lats1 or Lats2 did not affect the overall survival of the heterozygotes(Lats1:P=0.654;Lats2:P=0.152).Conclusion:These results indicate that a single allele of Lats1 or Lats2 may be sufficient for nor