A single copy of large tumor suppressor 1 or large tumor suppressor 2 is sufficient for normal hematopoiesis
A single copy of large tumor suppressor 1 or large tumor suppressor 2 is sufficient for normal hematopoiesis
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单个拷贝的大肿瘤抑制因子1或大肿瘤抑制因子2足以维持正常造血
DOI：
10.1097/cm9.0000000000000934
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发表时间：
2020-08
影响因子：
6.1
通讯作者：
Hou Yu
中科院分区：
文献类型：
--
作者：
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
摘要背景造血干细胞（HSCs）具有分化为所有血细胞亚群和自我更新的能力。大肿瘤抑制因子1（LATS 1）和大肿瘤抑制因子2（LATS 2）激酶对于细胞周期调节、生物体适应性、基因组完整性和癌症预防是必需的。在这里，我们研究了Lats1和Lats2是否对维持小鼠HSC的自我更新和静止能力至关重要。方法采用定量逆转录-聚合酶链反应（RT-PCR）方法检测Lats1和Lats2在骨髓祖细胞亚群和成熟骨髓细胞中的表达水平。使用成簇的规则间隔的短回文重复序列系统来产生Lats1或Lats2敲除小鼠。使用全血细胞计数比较Lats1或Lats2杂合子与同窝仔之间的白色血细胞、淋巴细胞、单核细胞、中性粒细胞和血小板的绝对数量。流式细胞术用于评估Lats1或Lats2杂合子和同窝仔中造血祖细胞（HPC）和HSC池的大小。采用Student t检验分析两组之间的比较。结果Lats1和Lats2在造血细胞中广泛表达，在原始造血细胞中的表达水平高于成熟造血细胞。产生Lats1或Lats2敲除小鼠，其中纯合子显示胚胎致死性。Lats1中HPC和HSC池的大小（HPC：野生型[WT] vs.杂合子，220，426.77 ± 54，384.796 vs. 221，149.4 ± 42，688.29，P = 0.988; HSC：WT与杂合子，2498.932 ± 347.856与3249.763 ± 370.412，P = 0.105）或Lats2（HPC：WT与杂合子，425，540.52 ± 99，721.86与467，127.8 ± 89，574.48，P = 0.527; HSC：野生型与杂合子，4760.545 ± 1518.01与5327.437 ± 873.297，P = 0.502）杂合子未受损。 此外，Lats1或Lats2的缺失并不影响杂合子的总生存率（Lats1：P = 0.654; Lats2：P = 0.152）。 结论Lats1或Lats2的单个等位基因可能足以维持正常造血。
Abstract Background Hematopoietic stem cells (HSCs) have the ability to differentiate into all subsets of blood cells and self-renew. Large tumor suppressor 1 (LATS1) and large tumor suppressor 2 (LATS2) kinases are essential for cell cycle regulation, organism fitness, genome integrity, and cancer prevention. Here, we investigated whether Lats1 and Lats2 are critical for the maintenance of the self-renewal and quiescence capacities of HSCs in mice. Methods 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 mice. Complete 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 littermates. Flow cytometry was used to assess the size of hematopoietic progenitor cells (HPCs) and HSC pools in Lats1 or Lats2 heterozygotes and littermates. The comparison between the two groups was analyzed using Student's t test. Results Lats1 and Lats2 were widely expressed in hematopoietic cells with higher expression levels in primitive hematopoietic cells than in mature cells. Lats1 or Lats2 knockout mice were generated, with the homozygotes showing embryonic lethality. The size of the HPC and HSC pools in Lats1 (HPC: wild-type [WT] vs. heterozygote, 220,426.77 ± 54,384.796 vs. 221,149.4 ± 42,688.29, P = 0.988; HSC: WT vs. heterozygote, 2498.932 ± 347.856 vs. 3249.763 ± 370.412, P = 0.105) or Lats2 (HPC: WT vs. heterozygote, 425,540.52 ± 99,721.86 vs. 467,127.8 ± 89,574.48, P = 0.527; HSC: WT vs. heterozygote, 4760.545 ± 1518.01 vs. 5327.437 ± 873.297, P = 0.502) heterozygotes were not impaired. Moreover, 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 normal hematopoiesis.
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影响因子：
64.8
作者：
通讯作者：
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Hippo 通路在器官大小控制、组织稳态和癌症中的作用
影响因子：
64.5
作者：
Yu FX;Zhao B;Guan KL
通讯作者：
Guan KL
影响因子：
50.3
作者：
Zhou D;Conrad C;Xia F;Park JS;Payer B;Yin Y;Lauwers GY;Thasler W;Lee JT;Avruch J;Bardeesy N
通讯作者：
Bardeesy N
影响因子：
8
作者：
Pan, Wei-Wei;Moroishi, Toshiro;Guan, Kun-Liang
通讯作者：
Guan, Kun-Liang
影响因子：
10.5
作者：
Zhao, Bin;Li, Li;Guan, Kun-Liang
通讯作者：
Guan, Kun-Liang