Mouse Bone Marrow
Mineral and Amino Acid Profiling of Different Hematopoietic Populations from the Mouse Bone Marrow
Steady hematopoiesis is essential for lifelong production of all mature blood cells. Hematopoietic stem and progenitor cells (HSPCs) found in the bone marrow ensure hematopoietic homeostasis in an organism. Failure of this complex process, which involves a fine balance of self-renewal and differentiation fates, often result in severe hematological conditions such as leukemia and lymphoma. Several molecular and metabolic programs, internal or in close interaction with the bone marrow niche, have been identified as important regulators of HSPC function. More recently, nutrient sensing pathways have emerged as important modulators of HSC homing, dormancy, and function in the bone marrow. Here we describe a method for reliable measurement of various amino acids and minerals in different rare bone marrow (BM) populations, namely HSPCs. We found that the amino acid profile of the most primitive hematopoietic compartments (KLS) did not differ significantly from the one of their direct progenies (common myeloid progenitor CMP), while granulocyte-monocyte progenitors (GMPs), on the opposite of megakaryocyte-erythroid progenitors (MEPs), have higher content of the majority of amino acids analyzed. Additionally, we identified intermediates of the urea cycle to be differentially expressed in the KLS population and were found to lower mitochondrial membrane potential, an established readout on self-renewal capability. Moreover, we were able to profile for the first time 12 different minerals and detect differences in elemental contents between different HSPC compartments. Importantly, essential dietary trace elements, such as iron and molybdenum, were found to be enriched in granulocyte-monocyte progenitors (GMPs). We envision this amino acid and mineral profiling will allow identification of novel metabolic and nutrient sensing pathways important in HSPC fate regulation.
M. Girotra, C. Monnard, T. Konz, F. Sizzano, L. Goulet, J. P. Godin, G. Coukos, S. Rezzi, and N. Vannini,Mineral and Amino Acid Profiling of Different Hematopoietic Populations from the Mouse Bone Marrow, International Journal of Molecular Sciences, 2020, 21, 6444.
Haematopoiesis is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. [https://en.wikipedia.org/wiki/Haematopoiesis]
Granulocyte-monocyte progenitor (GMP) cells play a vital role in the immune system by maturing into a variety of white blood cells, including neutrophils and macrophages,
Molybdenum in animals
Molybdenum-containing enzymes catalyze basic metabolic reactions in the nitrogen, sulfur, and carbon cycles. With the exception of the nitrogenase cofactor, molybdenum is incorporated into proteins as the molybdenum cofactor that contains a mononuclear molybdenum atom coordinated to the sulfur atoms of a pterin derivative named molybdopterin. Certain microorganisms can also utilize tungsten in a similar fashion. Molybdenum-cofactor-containing enzymes catalyze the transfer of an oxygen atom, ultimately derived from or incorporated into water, to or from a substrate in a two-electron redox reaction.
Kisker, C., Schindelin, H., Rees, D.C., Molybdenum-cofactor-containing enzymes: Structure and mechanism, Annual Review Of Biochemistry, 1997, 66, 233-267.
Molybdenum is an essential constituent of the enzymes xanthine oxidase and aldehyde oxidase which occur in the livers and intestines of animals, and of hepatic sulfite oxidase. Xanthine oxidase has been isolated from cows' milk. Molybdenum in milk is present mostly in the enzyme, xanthine oxidase; the level is influenced by the level of dietary molybdenum although the level of xanthine oxidase is not.
Mills, C. F. and Davis, G. K., Trace elements in Human and Animal Nutrition, Metrz, W. ed., 5th Ed., Academic Press, New York , 1987, 429.
Changes in haematology, blood mineral profile, ultra structure and superoxide dismutase activities in erythrocytes in hypophosphetemic buffaloes given excess molybdenum
Sharma, A. K., Randhawa, S. N. S., Uppal, S. K., and Ranjan, R., Changes in haematology, blood mineral profile, ultra structure and superoxide dismutase activities in erythrocytes in hypophosphetemic buffaloes given excess molybdenum, Indian Journal of Animal Sciences, 2014, 84, 516-519.
Haematological profile of subchronic oral toxicity of molybdenum in buffalo calves
Varun, Sharma, S., Sandhu, H. S., and Gosal, N. S., Haematological profile of subchronic oral toxicity of molybdenum in buffalo calves, Indian Journal of Animal Sciences, 2014, 84, 520-522.