Cellular reprogramming最新文献

Via retrospective isolation of clones using Rewind, Jain et al. identified primed states of cells that reprogram to induced pluripotent stem cells. Examining clones, they find that cells retain memory of over several rounds of cell division. Moreover, they show that extrinsic factors change the number of primed cells, suggesting that there exist diverse paths of reprogramming and states of priming.

Cloning by somatic cell nuclear transfer (SCNT) remained challenging for Rhesus monkeys, mostly due to its low efficiency and neonatal death. Genome-scale analyses revealed that monkey SCNT embryos displayed widespread DNA methylation and transcriptional alterations, thus including loss of genomic imprinting that correlated with placental dysfunction. The transfer of inner cell masses (ICM) from cloned blastocysts into ICM-depleted fertilized embryos rescued placental insufficiency and gave rise to a cloned Rhesus monkey that reached adulthood without noticeable abnormalities.

Cellular senescence is a state in which cells enter cell cycle arrest. However, senescent cells have the ability to secrete signaling molecules such as chemokines, cytokines, and growth factors. This secretory activity is an important feature of senescent cells, since the secreted factors impact the surrounding cellular microenvironment. Indeed, senescent cells and their secretome play a crucial role during limb development. However, whether the process of limb regeneration also relies on senescent cells remains unclear. Creation of a novel targeted depletion strategy that can eliminate senescent cells in the regenerating limb has now demonstrated an important role for senescent cells in limb regeneration. This role is linked to senescent cell-derived Wnt signaling. These findings reveal a previously unknown role for senescent cells during limb regeneration through Wnt signaling.

Mesenchymal stem cell (MSCs) therapy, as a rapidly developing area of medicine, holds great promise for the treatment of a variety of medical conditions. MSCs are multipotent stem cells that can be isolated from various tissues and could self-renew and differentiate. They secrete cytokines and trophic factors that create a regenerative microenvironment and have immunomodulatory properties. Although clinical trials have been conducted with MSCs in various diseases, concerns regarding the possibility of malignant transformation of these cells have been raised. The studies showed a higher rate of hematological malignancy and carcinogenesis in experimental models after MSC transplantation. The mechanisms underlying malignant transformation of MSCs are complex and not fully understood, but they are believed to involve the presence of special signaling molecules and alterations in cell behavior regulation pathways. Possible pathways that lead to MSCs' oncogenic transformation occur through two mechanisms: spontaneous and stimulated malignant transformation, including cell fusion, fusion proteins, and the tumor microenvironment. MSC-based therapies have the potential to revolutionize medicine, and addressing the issue of malignancy is crucial to ensure their safety and efficacy. Therefore, the purpose of the present review is to summarize the potential mechanisms of the malignant transformation of MSCs. [Figure: see text].

Our group generated two induced pluripotent stem cell (iPSC) lines for in vitro red blood cell (RBC) production from blood donors with extensively known erythrocyte antigen profiles. One line was intended to give rise to RBCs for transfusions in patients with sickle cell disease (SCD), while the other was developed to create RBC panel reagents. Two blood donors were selected based on their RBC phenotypes, further complemented by high-throughput DNA array analysis to obtain a more comprehensive erythrocyte antigen profile. Enriched erythroblast populations from the donors' peripheral blood mononuclear cells were reprogrammed into iPSCs using nonintegrative plasmid vectors. The iPSC lines were characterized and subsequently subjected to hematopoietic differentiation. iPSC PB02 and iPSC PB12 demonstrated in vitro and in vivo iPSC features and retained the genotype of each blood donor's RBC antigen profile. Colony-forming cell assays confirmed that iPSC PB02 and iPSC PB12 generated hematopoietic progenitors. These two iPSC lines were generated with defined erythrocyte antigen profiles, self-renewal capacity, and hematopoietic differentiation potential. With improvements in hematopoietic differentiation, these cells could potentially be more efficiently differentiated into RBCs in the future. They could serve as a complementary approach for obtaining donor-independent RBCs and addressing specific demands for blood transfusions.

The interplay between aging and immune system deterioration presents a formidable challenge to human health, especially in the context of a globally aging population. Aging is associated with a decline in the body's ability to combat infections and an increased risk of various diseases, underlining the importance of rejuvenating the immune system as a strategy for promoting healthier aging. In issue 628 of Nature (2024), Ross et al. present a compelling study that introduces a novel strategy for rejuvenating the aged immune system (Ross et al., 2024). By using antibodies to selectively eliminate "aberrant" hematopoietic stem cells (HSCs), this research opens new avenues for addressing age-related immune deterioration.