Human stem cell-derived blastoids display similar morphology and cell lineages to normal blastocysts. However, the ability to investigate their developmental potential is limited. Here, we construct ...cynomolgus monkey blastoids resembling blastocysts in morphology and transcriptomics using naive ESCs. These blastoids develop to embryonic disk with the structures of yolk sac, chorionic cavity, amnion cavity, primitive streak, and connecting stalk along the rostral-caudal axis through prolonged in vitro culture (IVC). Primordial germ cells, gastrulating cells, visceral endoderm/yolk sac endoderm, three germ layers, and hemato-endothelial progenitors in IVC cynomolgus monkey blastoids were observed by single-cell transcriptomics or immunostaining. Moreover, transferring cynomolgus monkey blastoids to surrogates achieves pregnancies, as indicated by progesterone levels and presence of early gestation sacs. Our results reveal the capacity of in vitro gastrulation and in vivo early pregnancy of cynomolgus monkey blastoids, providing a useful system to dissect primate embryonic development without the same ethical concerns and access challenges in human embryo study.
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•Generation of cynomolgus monkey blastoids using naive ESCs and optimized protocol•Monkey blastoids showed similar morphology and lineage composition to blastocysts•In vitro cultured monkey blastoids recapitulate gastrulation to three germ layers•In vivo transplantation of monkey blastoids triggers pregnancy with gestation sacs
Stem cell-based embryo models provide a useful system for studying early embryonic development. Li and colleagues reported the generation of cynomolgus monkey blastoids with similar characteristics to natural blastocysts. These blastoids possess the capacity of in vitro gastrulation with three germ-layer differentiation and in vivo early pregnancy with gestation sac.
A formal demonstration that mammalian pluripotent stem cells possess preimplantation embryonic cell-like (naive) pluripotency is the generation of chimeric animals through early embryo ...complementation with homologous cells. Whereas such naive pluripotency has been well demonstrated in rodents, poor chimerism has been achieved in other species including non-human primates due to the inability of the donor cells to match the developmental state of the host embryos. Here, we have systematically tested various culture conditions for establishing monkey naive embryonic stem cells and optimized the procedures for chimeric embryo culture. This approach generated an aborted fetus and a live chimeric monkey with high donor cell contribution. A stringent characterization pipeline demonstrated that donor cells efficiently (up to 90%) incorporated into various tissues (including the gonads and placenta) of the chimeric monkeys. Our results have major implications for the study of primate naive pluripotency and genetic engineering of non-human primates.
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Background: The long-term symptoms from COVID-19 (C19) infection in pts with cancer is not fully known. To monitor the evolution of this symptom burden over time, we designed and ...implemented a C19-specific patient-reported outcome (PRO) measure that integrated with a known measure of cancer symptom burden. Methods: Within the institutional initiative on C19 and cancer named Data-Driven Determinants for C19 Oncology Discovery Effort (D3CODE), pts with cancer & PCR-pos C19 are invited to participate in this longitudinal study. Pts complete the EQ-5D-5L, the 13 symptom severity & 6 interference items of the core MD Anderson Symptom Inventory (MDASI)+14 COVID-specific items, all scored on a 0-10 scale, 0 = none, 10 = worst imaginable. Pts complete the survey daily x 14 days from positive test date, then weekly x 3months, then monthly x 2yrs. Demographic and disease information was collected. Psychometric procedures determined validity and reliability of the MDASI-COVID. Results: Between 5/15/20 – 02/14/21, 2154 pts w PCR-confirmed C19 were invited to participate in the longitudinal study. 1282 (60%) pts provided consent and began the longitudinal completion of PRO surveys. Pts were 54.5% Female and 45.5% Male, median age 59 years (range 15 – 92). 1021 (80%) are White/Caucasian, 206 (16%) Hispanic, 113 (9%) African American, and 39 (3%) Asian. The validation analysis of MDASI-COVID instrument included the 1
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600 pts where the mean overall health rating on EQ-5D-5L was 78.3 (SD 19.6), best being 100. Highest mean (M) severity symptoms on the MDASI-COVID were fatigue (M 3.45, SD 2.17), drowsiness (M 2.50, SD 2.89), sleep disturbance (M 2.44, SD 2.99), malaise (M 2.37, SD 3.05), and distress (M 2.27, SD 2.90). Most severe (≥ 7) symptoms) reported were fatigue (21.3% of pts), change in taste (14.8%), change in smell (14.4%), malaise (14.3%), sleep disturbance (14.3%), and drowsiness (14%). showed internal consistency (Cronbach α) of the 27 symptom items was 0.957, of the 6 interference items was 0.937. Mean severity of the 27 symptom items was significantly correlated with overall EQ-5D-5L health rating (correlation = -0.45, P < 0.0005), demonstrating concurrent validity. Mean symptom severity and interference showed known-group validity between pts who required hospitalization (symptom M 2.32, SD 2.09; interference M 3.29, SD 3.02) and those who did not (symptom M 1.69, SD 1.85; interference M 2.20, SD 2.64) (symptom P 0.007; interference P 0.004). Conclusions: We successfully deployed a PRO-based long-term symptom monitoring platform for pts with C19 and cancer. The validation analysis of this novel C19 specific PRO, the MDASI-COVID, aids in the quantification of the global symptom burden in pts with both cancer and COVID-19 infection. Deployment of this measure in the ongoing longitudinal observational cohort allows for in-depth understanding of the long-term symptoms related to C19 and cancer.
The longest vertical profile from the western basin of Taihu Lake ever taken was nearly 4 m (396 cm) in length and represented a time period of over 14 000 years. The core was analyzed for the ...following proxies, magnetic susceptibility, organic carbon isotope, total organic carbon, total nitrogen, total pigments, saturated hydrocarbons, carbon 14, thermolytic hydrogen (the hydrogen index, HI) and foraminifera. Results from the west Taihu lake core indicate that ca. 14 300-13 400 a B.P., the lake was relatively shallow and the climate was likely to have been quite arid. From 13 400 to 12 400 a B.P., the environment became less arid and the depth of the water in Lake Taihu increased. Marine incursions occurred during this period as indicated by the presence of numerous marine foraminifera. From ca. 12 400 to 10 900 a B.P., the climate became wetter, warmer and more variable. A cold dry period occurred around ca. 11 500 a B.P., causing the lake to become more shallow. From 10 900 to 10 000 a B.P., a warm and wet period reasserted itself and water depth again increased. A cold dry period reoccurred from 10 000 to 9500 a B. P. From 9500 to 7200 a B.P., the climate was quite variable. By 7200-5700 a B.P., the climate again turned warmer and wetter. Some of the major sediment proxies used in this study changed dramatically at ca. 5050 a B.P., reflecting changes in material source and a probable interruption of sedimentation. The modern environment (4900 aB.P.-present) was characterized by a well oxidized sediment layer and thriving algae. The lake is presently very eutrophic and is characterized by cyanobacteria, primarily Microcystis aeruginosa, the dominant primary producer in the lake. This is the first study to use a variety of organic geochemical proxies to infer paleoenvironmental changes in Taihu Lake.
