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Mammalian stem cells govern development, tissue homeostasis, and regeneration. Following years of study, their functions have been delineated with increasing precision. The past decade has witnessed heightened widespread use of stem cell terminology in association with durable T cell responses to infection, antitumor immunity, and autoimmunity. Interpreting this literature is complicated by the fact that descriptions are diverse and criteria for labeling 'stem-like' T cells are evolving. Working under the hypothesis that conceptual frameworks developed for actual stem cells can be used to better evaluate and organize T cells described to have stem-like features, we outline widely accepted properties of stem cells and compare these to different 'stem-like' CD4 + T cell populations., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The molecular mechanisms leading to the establishment of immunological memory are inadequately understood, limiting the development of effective vaccines and durable antitumor immune therapies. Here, we show that ectopic OCA-B expression is sufficient to improve antiviral memory recall responses, while having minimal effects on primary effector responses. At peak viral response, short-lived effector T cell populations are expanded but show increased Gadd45b and Socs2 expression, while memory precursor effector cells show increased expression of Bcl2 , Il7r, and Tcf7 on a per-cell basis. Using an OCA-B mCherry reporter mouse line, we observe high OCA-B expression in CD4 + central memory T cells. We show that early in viral infection, endogenously elevated OCA-B expression prospectively identifies memory precursor cells with increased survival capability and memory recall potential. Cumulatively, the results demonstrate that OCA-B is both necessary and sufficient to promote CD4 T cell memory in vivo and can be used to prospectively identify memory precursor cells., Competing Interests: Competing interests statement:The authors declare no competing interest.

The transition between pluripotent and tissue-specific states is a key aspect of development. Understanding the pathways driving these transitions will facilitate the engineering of properly differentiated cells for experimental and therapeutic uses. Here, we showed that during mesoderm differentiation, the transcription factor Oct1 activated developmental lineage-appropriate genes that were silent in pluripotent cells. Using mouse embryonic stem cells (ESCs) with an inducible knockout of Oct1, we showed that Oct1 deficiency resulted in poor induction of mesoderm-specific genes, leading to impaired mesodermal and terminal muscle differentiation. Oct1-deficient cells exhibited poor temporal coordination of the induction of lineage-specific genes and showed inappropriate developmental lineage branching, resulting in poorly differentiated cell states retaining epithelial characteristics. In ESCs, Oct1 localized with the pluripotency factor Oct4 at mesoderm-associated genes and remained bound to those loci during differentiation after the dissociation of Oct4. Binding events for Oct1 overlapped with those for the histone lysine demethylase Utx, and an interaction between Oct1 and Utx suggested that these two proteins cooperate to activate gene expression. The specificity of the ubiquitous Oct1 for the induction of mesodermal genes could be partially explained by the frequent coexistence of Smad and Oct binding sites at mesoderm-specific genes and the cooperative stimulation of mesodermal gene transcription by Oct1 and Smad3. Together, these results identify Oct1 as a key mediator of mesoderm lineage-specific gene induction.

Numerous precipitation methods for creating nanoparticle dispersions that are based on mixing a solution with a miscible nonsolvent have been developed. Here, we show that for polymer particles, the formation is highly dependent on the rate of mixing. We also demonstrate the importance of the glass transition of the polymers on particle formation. A simple model of droplet formation during mixing provides a satisfactory description of the observed dependence of particle size on polymer molecular weight, concentration, solvent ratio, and mixing conditions.

Electrocoagulation is an effective treatment modality for localized cancer of the distal rectum. Proper selection remains the key to successful treatment. Of potentially curable patients with cancer of the rectum followed up for a median of five years, 69 per cent had no evidence of cancer at the end of the study period. Gross tumor morphology defined two distinct groups with regard to outcome after electrocoagulation. Ninety-two per cent of patients with polypoid/exophytic tumors as compared to 33 per cent of patients with ulcerative lesions had successful treatment. Based on these results, the authors believe that lesions that are exophytic represent early cancers with a low incidence of nodal spread and, as such, can be treated by electrocoagulation with confidence. As a palliative measure, the the authors found electrocoagulation to yield equivocal results.