Type 2 transglutaminase (TG2) is a multifunctional protein involved in various biological processes playing a key regulatory role in cell homeostasis such as cell death and autophagy. New evidence is emerging that support an important role of autophagy in regulating normal hematopoiesis. Prompted by these findings, in this study we investigated in vivo involvement of TG2 in mouse hematopoiesis under normal or nutrient deprivation conditions. We found that the number and rate of differentiation of bone marrow hematopoietic stem cell was decreased in the TG2 knockout mice. We present evidence showing that these effects on hematopoietic system are very likely due to the TG2-dependent impairment of autophagy. In fact, stimulation of autophagy by starvation is able to rescue the block of the differentiation of stem cells progenitors in the TG2 KO mice. It was also shown that the RhoA/ERK½ pathway, known to be essential for regulation of the bone marrow progenitor cells homeostasis, was significantly impaired in the absence of TG2. Hence, this study expanded our knowledge about TG2 discovering a role of this enzyme in regulation of hematopoiesis.

中文翻译：

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2 型转谷氨酰胺酶参与造血干细胞稳态

2 型转谷氨酰胺酶 (TG2) 是一种多功能蛋白质，参与各种生物过程，在细胞内稳态（如细胞死亡和自噬）中起关键调节作用。新的证据支持自噬在调节正常造血中的重要作用。在这些发现的推动下，在本研究中，我们调查了 TG2 在正常或营养缺乏条件下在小鼠造血中的体内参与。我们发现TG2基因敲除小鼠骨髓造血干细胞的分化数量和分化率降低。我们提供的证据表明，这些对造血系统的影响很可能是由于自噬的 TG2 依赖性损伤。事实上，饥饿刺激自噬能够挽救 TG2 KO 小鼠中干细胞祖细胞分化的阻断。研究还表明，已知对调节骨髓祖细胞稳态至关重要的 RhoA/ERK1/2 通路在没有 TG2 的情况下显着受损。因此，这项研究扩展了我们关于 TG2 的知识，发现了这种酶在调节造血中的作用。