Transglutaminase Type 2 is Involved in the Hematopoietic Stem Cells Homeostasis

Area of Science:

• Molecular Biology
• Cell Biology
• Hematology

Background:

• Type 2 transglutaminase (TG2) is a key regulator of cellular processes, including cell death and autophagy.
• Autophagy plays a critical role in maintaining normal hematopoiesis.
• The precise role of TG2 in hematopoiesis remains largely unexplored.

Purpose of the Study:

• To investigate the in vivo role of TG2 in mouse hematopoiesis under normal and nutrient-deprived conditions.
• To elucidate the mechanisms underlying TG2's influence on hematopoietic stem cells and progenitors.

Main Methods:

• Comparison of hematopoiesis in wild-type and TG2 knockout mice.
• Assessment of hematopoietic stem cell number and differentiation rates.
• Evaluation of autophagy modulation via nutrient deprivation (starvation).
• Analysis of the RhoA/ERK1/2 signaling pathway.

Main Results:

• TG2 knockout mice exhibited reduced numbers and impaired differentiation of bone marrow hematopoietic stem cells.
• Autophagy stimulation through starvation rescued the differentiation block in TG2 knockout stem cell progenitors.
• The RhoA/ERK1/2 pathway, crucial for progenitor cell homeostasis, was significantly impaired in TG2-deficient mice.

Conclusions:

• TG2 plays a significant role in regulating hematopoiesis.
• TG2-dependent autophagy is essential for normal hematopoietic stem cell differentiation and bone marrow homeostasis.
• This study reveals a novel function of TG2 in the regulation of the hematopoietic system.