论文部分内容阅读
Background::Hematopoietic stem cells (HSCs) have the ability to differentiate into all subsets of blood cells and self-renew. Large tumor suppressor 1 (n LATS1) and large tumor suppressor 2 (n LATS2) kinases are essential for cell cycle regulation, organism fitness, genome integrity, and cancer prevention. Here, we investigated whether n Lats1 and n Lats2 are critical for the maintenance of the self-renewal and quiescence capacities of HSCs in mice.n Methods::Quantitative reverse transcription-polymerase chain reaction was used to determine the expression levels of n Lats1 and n Lats2 in subsets of progenitor cells and mature bone marrow cells. A clustered regularly interspaced short palindromic repeats system was used to generate n Lats1 or n Lats2 knockout mice. Complete blood cell counts were used to compare the absolute number of white blood cells, lymphocytes, monocytes, neutrophils, and platelets between n Lats1 or n Lats2 heterozygotes and littermates. Flow cytometry was used to assess the size of hematopoietic progenitor cells (HPCs) and HSC pools in n Lats1 or n Lats2 heterozygotes and littermates. The comparison between the two groups was analyzed using Student’s n t test.n Results::Lats1 and n Lats2 were widely expressed in hematopoietic cells with higher expression levels in primitive hematopoietic cells than in mature cells. n Lats1 or n Lats2 knockout mice were generated, with the homozygotes showing embryonic lethality. The size of the HPC and HSC pools in n Lats1 (HPC: wild-type [WT] n vs. heterozygote, 220,426.77 ± 54,384.796 n vs. 221,149.4 ± 42,688.29, n P = 0.988; HSC: WT n vs. heterozygote, 2498.932 ± 347.856 n vs. 3249.763 ± 370.412, n P = 0.105) n or Lats2 (HPC: WT n vs. heterozygote, 425,540.52 ± 99,721.86 n vs. 467,127.8 ± 89,574.48, n P = 0.527; HSC: WT n vs. heterozygote, 4760.545 ± 1518.01 n vs. 5327.437 ± 873.297, n P = 0.502) heterozygotes were not impaired. Moreover, the depletion of n Lats1 or n Lats2 did not affect the overall survival of the heterozygotes (n Lats1: n P = 0.654; n Lats2: n P = 0.152).n Conclusion::These results indicate that a single allele of n Lats1 or n Lats2 may be sufficient for normal hematopoiesis.n