TY - JOUR

T1 - Stimulation of mouse hematopoietic stem cells by angiogenin and DNA preparations

AU - Potter, E A

AU - Dolgova, E V

AU - Proskurina, A S

AU - Ruzanova, V S

AU - Efremov, Y R

AU - Kirikovich, S S

AU - Oshikhmina, S G

AU - Mamaev, A L

AU - Taranov, O S

AU - Bryukhovetskiy, A S

AU - Grivtsova, L U

AU - Kolchanov, N A

AU - Ostanin, A A

AU - Chernykh, E R

AU - Bogachev, S S

N1 - This research was funded by the Ministry of Science and Higher Education of the Russian Federation via the Institute of Cytology and Genetics (State Budget Project No. FWNR-2022-0016). The authors are also grateful to Inga N. Zajceva and Alexey A. Purtov for additional funding.

PY - 2024

Y1 - 2024

N2 - Immature hematopoietic progenitors are a constant source for renewal of hemocyte populations and the basic component of the tissue and cell repair apparatus. A unique property of these cells of internalizing extracellular double-stranded DNA has been previously shown. The leukostimulatory effect demonstrated in our pioneering studies was considered to be due to the feature of this cell. In the present research, we have analyzed the effects of DNA genome reconstructor preparation (DNAgr), DNAmix, and human recombinant angiogenin on both hematopoietic stem cells and multipotent progenitors. Treatment with bone marrow cells of experimental mice with these preparations stimulates colony formation by hematopoietic stem cells and proliferation of multipotent descendants. The main lineage responsible for this is the granulocyte-macrophage hematopoietic lineage. Using fluorescent microscopy as well as FACS assay, co-localization of primitive c-Kit- and Sca-1-positive progenitors and the TAMRA-labeled double-stranded DNA has been shown. Human recombinant angiogenin was used as a reference agent. Cells with specific markers were quantified in intact bone marrow and colonies grown in the presence of inducers. Quantitative analysis revealed that a total of 14,000 fragment copies of 500 bp, which is 0.2% of the haploid genome, can be delivered into early progenitors. Extracellular double-stranded DNA fragments stimulated the colony formation in early hematopoietic progenitors from the bone marrow, which assumed their effect on cells in G0. The observed number of Sca1+/c-Kit+ cells in colonies testifies to the possibility of both symmetrical and asymmetrical division of the initial hematopoietic stem cell and its progeny.

AB - Immature hematopoietic progenitors are a constant source for renewal of hemocyte populations and the basic component of the tissue and cell repair apparatus. A unique property of these cells of internalizing extracellular double-stranded DNA has been previously shown. The leukostimulatory effect demonstrated in our pioneering studies was considered to be due to the feature of this cell. In the present research, we have analyzed the effects of DNA genome reconstructor preparation (DNAgr), DNAmix, and human recombinant angiogenin on both hematopoietic stem cells and multipotent progenitors. Treatment with bone marrow cells of experimental mice with these preparations stimulates colony formation by hematopoietic stem cells and proliferation of multipotent descendants. The main lineage responsible for this is the granulocyte-macrophage hematopoietic lineage. Using fluorescent microscopy as well as FACS assay, co-localization of primitive c-Kit- and Sca-1-positive progenitors and the TAMRA-labeled double-stranded DNA has been shown. Human recombinant angiogenin was used as a reference agent. Cells with specific markers were quantified in intact bone marrow and colonies grown in the presence of inducers. Quantitative analysis revealed that a total of 14,000 fragment copies of 500 bp, which is 0.2% of the haploid genome, can be delivered into early progenitors. Extracellular double-stranded DNA fragments stimulated the colony formation in early hematopoietic progenitors from the bone marrow, which assumed their effect on cells in G0. The observed number of Sca1+/c-Kit+ cells in colonies testifies to the possibility of both symmetrical and asymmetrical division of the initial hematopoietic stem cell and its progeny.

KW - Humans

KW - Animals

KW - Mice

KW - Hematopoietic Stem Cells

KW - Ribonuclease, Pancreatic/pharmacology

KW - Bone Marrow Cells

KW - DNA

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85187107178&origin=inward&txGid=0f555a1e8dc59733ac08fa41e333910a

U2 - 10.1590/1414-431X2024e13072

DO - 10.1590/1414-431X2024e13072

M3 - Article

C2 - 38451606

VL - 57

JO - Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas

JF - Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas

SN - 0100-879X

M1 - e13072

ER -