Cellular reprogramming最新文献

Tracheal reconstruction is necessary in patients with large tracheal defects. Previously, artificial tracheae made of polypropylene and collagen sponge have been used clinically by our group. As a basic research aimed at promoting epithelialization for infection defense, we transplanted cell sheets of human induced pluripotent stem cell (hiPSC)-derived airway epithelial cells (iAECs) with artificial tracheae into tracheal defects of rats and confirmed their engraftment. In this study, we examined the difference in the cell engraftment between hiPSC-derived airway epithelial progenitor cells (iAEPCs) and iAECs. Cell sheets were collected on days 38, 45, and 56 of induction into iAECs, then transplanted into nude rats with tracheal defects along with the artificial trachea. Two weeks after transplantation, surviving human nuclear antigen (HNA)-positive epithelial cells were observed none of six rats in the 38-day group, two out of six in 45-day group, and five out of six in the 56-day group. The proportion of surviving HNA+ cells among the epithelial cells of 56-day group was significantly higher those of 38-day group. Differentiated iAECs are more suitable for the transplantation of hiPSCs into tracheal defects. Our findings propose the use of differentiated cells for improvement of engraftment efficiency.

Cord blood (CB) is widely stored as a source of hematopoietic stem cells for potential future use, though its application for autologous purposes remains limited. Repurposing CB into human-induced pluripotent stem cells (hiPSCs) can broaden its utility beyond hematological conditions. This study investigated the effects of umbilical cord-mesenchymal stromal cell (UC-MSC) co-culture on CB CD34⁺ cells and the characteristics of the resulting hiPSCs. CD34⁺ cells were isolated, expanded in UC-MSC co-culture for 3 days, and reprogrammed into hiPSCs using episomal vectors. Results showed that UC-MSC co-culture significantly increased CD34⁺ cell numbers (p < 0.0001, n = 6), with a reduced population doubling time of 25.1 ± 2.1 hours compared with the control (p < 0.0004, n = 6). The yield of CD34⁺ cells was substantially higher in the UC-MSC co-culture group. The hiPSCs exhibited comparable reprogramming efficiency, pluripotency marker expression, trilineage differentiation potential, and genomic stability to CD34⁺ cells expanded under standard culture conditions. These findings suggest that CD34⁺ cells from CB, expanded in UC-MSC co-culture, can be reprogrammed into functional hiPSCs without compromising cell quality or genetic stability.

The successful generation of long-term engrafting hematopoietic stem cells (HSCs) from human-induced pluripotent stem cells (hiPSCs) has long been sought to revolutionize treatments for hematological disorders, eliminating reliance on donors and avoiding immune rejection, and thus has been seen as a major milestone in regenerative medicine. Previous studies, guided by developmental hematopoiesis, made progress in creating blood cells from hiPSCs, but challenges persisted in producing hematopoietic cells with functional properties of genuine HSCs capable of long-term engraftment. In their recent study, Ng and colleagues described an optimized differentiation protocol that manipulates key signaling pathways, including TGF-β, WNT, BMP, and retinoic acid in a stage-specific manner to generate HSCs with multilineage capacity. This strategy yielded hematopoietic cells capable of engrafting long term with high levels of human chimerism in recipient mice. This research provides a blueprint for future studies aiming for personalized HSC-based therapies for various blood disorders.

Tumors evade immune detection by downregulating antigen presentation and hindering immune responses. Type 1 conventional dendritic cells (cDC1s) are vital in stimulating cytotoxic T cells against tumors. Ascic et al. are now demonstrating the in situ ability of PU.1, IRF8, and BATF3 (PIB) transcription factors to directly reprogram a plethora of tumors bypassing the suppressive effects of the tumor microenvironment, and leading to overall tumor regression while eliciting a systemic immune response that can protect from secondary tumor induction.

Spermatogenesis constitutes a complex and intricate cascade of differentiation, indispensable for the male reproductive competence. The intercellular communication conduits of Sertoli cells (SCs) are pivotal in orchestrating this cascade ensuring sustenance and development of germ cells. Single cells and bioinformatics recently demonstrated articles are used for the regulatory modalities through which SCs modulate spermatogenesis, specifically via androgen receptors (ARs), the transforming growth factor-beta/Smad axis, mitogen-activated protein kinases, cAMP/protein kinase A (PKA), phosphatidylinositol 4,5-bisphosphate 3-kinase (PI3k)/AKT serine threonine kinase (Akt), AMP-activated protein kinase, and AR pathways. Within this framework, homeostasis of gap junction dynamics, cryptic sites and the activities at tight junctions and adherens junctions, with the integrity of the testicular barrier, glucose assimilation, lactate distribution, being governed also along with SC maturation. Disruptions in activities or abnormal concentration in derangements in AR, cAMP/PKA, and PI3k/Akt pathways, and as well as the molecules that comprise them, would present male infertility.

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.