Biology subjects

Domen, J.

Publications and source records attributed to Domen, J..

3 recordsLinked to original sources

bioRxiv2026

Human Haematopoietic Stem Cells released into circulation following mobilization express multiple G0-associated quiescence markers

Haematopoietic stem cells (HSC), while usually quiescent, can rapidly divide following specific stimuli (mobilization). These HSC can seed additional niches, allowing for the swift generation of essential blood cells. However, studies in mice and humans have clearly demonstrated that cycling bone marrow (BM) HSC (cells in the G1/S/G2/M phases) engraft and reconstitute the haematopoietic system poorly compared with HSC in the G0 phase1. This raises the question why mobilized HSC, immediately following 3 or more cell divisions2, efficiently reconstitute the haematopoietic system. We studied this phenomenon in human HSC using scRNAseq analysis. We found that mobilized HSC rapidly start transcribing genes associated with quiescence, specific for the G0 phase of the cell cycle. We hypothesize that this rapid switch from actively dividing to quiescent cells combined with our extensive RNA expression data will allow us to better define pathways involved in this process.

Cell Biology↗

bioRxiv2025

Graft protection by myeloid progenitor cells using lethal or non-lethal preconditioning.

Myeloid progenitor cell (MPC) therapy can protect against infection and can be used as an irradiation countermeasure, but can also prevent rejection of matched grafts. Here we report on the matching requirements between MPCs and skin grafts, and on the development of a non-lethal preconditioning model that supports MPC-induced protection of skin grafts. Mouse MPCs (mMPC) were obtained from HSC following 10-day ex vivo expansion. Skin grafts were tested in host mice that either received a lethal dose of irradiation and reconstitution with allogeneic mMPC and third party HSCs or were given injections with depleting antibodies and chemotherapeutics followed by transplantation of mMPC without HSC. mMPC-matched grafts were protected and no significant difference was observed between mice receiving irradiation and fully matched grafts (major and minor transplantation antigens), partially matched grafts (major only), and fully matched grafts in mice that received sublethal irradiation. Haploidentical grafts (half of the MHC alleles not matched at all) are not protected. We conclude that closely matched mMPCs are sufficient to prevent rejection. We also show that mMPCs are effective in a trachea transplant model. Graft protection does not require either lethal preconditioning or an accompanying HSC transplantation, and affects both T- and B-cell responses.

immunology↗

bioRxiv2025

Electrical Stimulation Rejuvenates Tunicates: Altered Stem Cell and Immune Activity

Applicable methods of rejuvenating organisms and improving resistance to environmental stimuli are needed. During attempts to synchronize heart rates in unhealthy colonial chordates, we observed morphological rejuvenation. While the importance of endogenously generated bioelectric currents in development is well-established1,2, and exogenously applied current has shown promise in regenerative medicine3,4,5,6,7,8,9, a model that robustly increases longevity and fertility while providing detailed mechanistic insights has not been reported. Here, we report the establishment of such a model using pulsatile electrical current (PEC) in Botryllus schlosseri, an established colonial chordate model10,11,12,13,14,15. PEC treatment significantly improved survival, morphological integrity, stem cell mediated regeneration, and gonad production in Botryllus. Transcriptomic analysis revealed pathway changes associated with cellular metabolism, cell cycle, stem cell activity, DNA repair, and immune modulation. Notably, PEC-induced expression patterns resemble the exercise-induced macrophage-associated transcriptional response previously observed across several mammalian species16,17. This transcriptomic signature correlated with an increase in immune-cell-containing populations. These findings demonstrate that PEC can improve longevity, vitality, and reproduction in an established model renowned for defining broadly applicable biological principles. These studies offer insights into novel strategies for promoting healthy aging and organismal survival.

developmental biology↗