Human post-implantation blastocyst-like characteristics of Muse cells isolated from human umbilical cord.

Muse cells, identified as cells positive for the pluripotent surface marker SSEA-3, are pluripotent-like endogenous stem cells located in the bone marrow (BM), peripheral blood, and organ connective tissues. The detailed characteristics of SSEA-3(+) cells in extraembryonic tissue, however, are unknown. Here, we demonstrated that similar to human-adult tissue-Muse cells collected from the BM, adipose tissue, and dermis as SSEA-3(+), human-umbilical cord (UC)-SSEA-3(+) cells express pluripotency markers, differentiate into triploblastic-lineage cells at a single cell level, migrate to damaged tissue, and exhibit low telomerase activity and non-tumorigenicity. Notably, ~ 20% of human-UC-SSEA-3(+) cells were negative for X-inactive specific transcript (XIST), a naïve pluripotent stem cell characteristic, whereas all human adult tissue-Muse cells are XIST-positive. Single-cell RNA sequencing revealed that the gene expression profile of human-UC-SSEA-3(+) cells was more similar to that of human post-implantation blastocysts than human-adult tissue-Muse cells. The DNA methylation level showed the same trend, and notably, the methylation levels in genes particularly related to differentiation were lower in human-UC-SSEA-3(+) cells than in human-adult tissue-Muse cells. Furthermore, human-UC-SSEA-3(+) cells newly express markers specific to extraembryonic-, germline-, and hematopoietic-lineages after differentiation induction in vitro whereas human-adult tissue-Muse cells respond only partially to the induction. Among various stem/progenitor cells in living bodies, those that exhibit properties similar to post-implantation blastocysts in a naïve state have not yet been found in humans. Easily accessible human-UC-SSEA-3(+) cells may be a valuable tool for studying early-stage human development and human reproductive medicine.

Full-length plasma skeletal muscle myosin isoform deficiency is associated with coagulopathy in acutely injured patients.

BACKGROUND: Skeletal muscle myosin (SkM) molecules are procoagulant both in vitro and in vivo. The association of plasma SkM isoforms with blood coagulability and hemostatic capacity has not been defined. OBJECTIVES: We hypothesized that coagulopathy in acutely injured patients is associated with procoagulant plasma SkM heavy chain levels. METHODS: To test this hypothesis, citrated whole blood and plasma from 104 trauma patients were collected and studied to obtain data for rapid thrombelastography, international normalized ratios, and plasma SkM levels. Coagulability parameters were dichotomized by the threshold for the hypercoagulable trauma-induced coagulopathy. RESULTS: Lower plasma full-length SkM heavy chain (full-SkM) levels were associated with higher international normalized ratio values (>1.3) (p = .03). The full-SkM levels were also associated with a lower rate of clot propagation (thrombelastography angle <65°) (p = .004), and plasma full-SkM levels were positively correlated with the thrombelastography angle (r2  = .32, p = .0007). The trauma patient group with the lower plasma full-SkM levels showed an association with lower clot strength (maximum amplitude <55 mm) (p = .002), and plasma full-SkM levels positively correlated with maximum amplitude (r2  = .27, p = .005). Hyperfibrinolysis was associated with significantly decreased full-SkM levels (p = .03). Trauma patients who required red blood cells and fresh frozen plasma transfusions had lower plasma full-SkM levels compared with those without transfusions (p = .04 and .02, respectively). CONCLUSIONS: In acutely injured trauma patients, lower levels of plasma full-SkM levels are linked to hypocoagulability in trauma-induced coagulopathy, implying that SkM plays a role in the hemostatic capacity in trauma patients and may contribute to trauma-induced coagulopathy.

Plasma skeletal muscle myosin phenotypes identified by immunoblotting are associated with pulmonary embolism occurrence in young adults.

BACKGROUND: Purified skeletal muscle myosin (SkM) binds factor Xa and is procoagulant. The molecular forms of SkM in human plasma have not been characterized. METHOD: Human plasma SkM heavy chain (HC) isoforms of different molecular weights were detected by a newly developed immunoblotting protocol. In this pilot study, the distribution of SkM HC antigen isoforms in plasmas of healthy subjects and young adult patients with venous thrombosis was analyzed. RESULTS: Multiple SkM HC antigen bands were detected in human plasmas, corresponding to full-length SkM HC, heavy meromyosin, or the S1 fragment. Plasma immunoblots of healthy subjects displayed three major phenotypes: Type I with two primary bands for full-length SkM and heavy meromyosin, and two lesser bands including S1 fragment (54%); Type II with bands primarily for full-length SkM HC (34%); and Type III with only a band for the S1 fragment (12%). Plasma SkM HC antigen Type II phenotype was associated with an increased occurrence of isolated pulmonary embolism in younger patients, respectively (≤50 years old). CONCLUSIONS: Three SkM HC antigen phenotypes were identified in human plasma by immunoblotting, and Type II phenotype was correlated with the occurrence of isolated pulmonary embolisms in younger patients.