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1.
J Mater Chem B ; 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32022083

RESUMO

Analysis of circulating tumor cells (CTCs) can provide significant clinical information for tumors, which has proven to be helpful for cancer diagnosis, prognosis monitoring, treatment efficacy, and personalized therapy. However, CTCs are an extremely rare cell population, which challenges the isolation of CTCs from patient blood. Over the last few decades, many strategies for CTC detection have been developed based on the physical and biological properties of CTCs. Among them, nanostructured interfaces have been widely applied as CTC detection platforms to overcome the current limitations associated with CTC capture. Furthermore, aptamers have attracted significant attention in the detection of CTCs due to their advantages, including good affinity, low cost, easy modification, excellent stability, and low immunogenicity. In addition, effective and nondestructive release of CTCs can be achieved by aptamer-mediated methods that are used under mild conditions. Herein, we review some progress in the detection and release of CTCs through aptamer-functionalized nanostructured interfaces.

2.
Opt Lett ; 45(3): 767, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32004306

RESUMO

In this erratum the set of Eqs. (2a) and (2b), Eqs. (4) and (5), and the corresponding figure and values in the text of Opt. Lett.45, 4215 (2019)OPLEDP0146-959210.1364/OL.44.004215 have been updated.

3.
Soft Matter ; 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32051977

RESUMO

Inorganic-organic co-assembly of anionic polyoxometalates (POMs) with zwitterions provides a facile way to fabricate functional soft materials. In this paper, a translucent, photoluminescent polymer hydrogel was fabricated from Weakley-type POM Na9EuW10O36 (EuW10) and polymerizable imidazole-type zwitterion 3-(1-vinyl-3-imidazolio)propanesulfonate (VIPS) via a one-step synthesis method. Detailed characterization indicated that the polymerization of double bonds in VIPS and electrostatic interactions between EuW10 and VIPS play important roles in the formation of the hydrogels. Additionally, the introduction of non-polymerizable zwitterions 3-(1-methyl-3-imidazolio)propanesulfonate (MIPS) or 3-(1-decyl-3-imidazolio)propanesulfonate (C10IPS) can improve the mechanical and luminous performances of the hydrogels. Especially, C10IPS with a long alkyl chain would more significantly alter the coordination environment of EuW10, and consequently resulted in a more efficient energy transfer process. Further investigations revealed that the chemical environment around the Eu3+ can be highly influenced by organic solvents with stronger coordination abilities than water molecules, such as acetone. The translucency and luminescence intensity of the hydrogels can be reversibly transformed after alternately immersing in acetone or H2O for several minutes. Our results provided a useful strategy for the fabrication of luminescent hydrogels by regulating the noncovalent interactions between POMs and zwitterions.

4.
Hypertension ; : HYPERTENSIONAHA11914041, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31957522

RESUMO

Aldosterone-producing adenomas (APAs) are one of the main causes of primary aldosteronism and the most prevalent surgically correctable form of hypertension. Aldosterone-producing cell clusters (APCCs) comprise tight nests of zona glomerulosa cells, strongly positive for CYP11B2 (aldosterone synthase) in immunohistochemistry. APCCs have been suggested as possible precursors of APAs because they frequently carry driver mutations for constitutive aldosterone production, and a few adrenal lesions with histopathologic features of both APCCs and APAs have been identified. Our objective was to investigate the metabolic phenotypes of APCCs (n=27) compared with APAs (n=6) using in situ matrix-assisted laser desorption/ionization mass spectrometry imaging of formalin-fixed paraffin-embedded adrenals from patients with unilateral primary aldosteronism. Specific distribution patterns of metabolites were associated with APCCs and classified 2 separate APCC subgroups (subgroups 1 and 2) indistinguishable by CYP11B2 immunohistochemistry. Metabolic profiles of APCCs in subgroup 1 were tightly clustered and distinct from subgroup 2 and APAs. Multiple APCCs from the same adrenal displayed metabolic profiles of the same subgroup. Metabolites of APCC subgroup 2 were highly similar to the APA group and indicated enhanced metabolic pathways favoring cell proliferation compared with APCC subgroup 1. In conclusion, we demonstrate specific subgroups of APCCs with strikingly divergent distribution patterns of metabolites. One subgroup displays a metabolic phenotype convergent with APAs and may represent the progression of APCCs to APAs.

5.
Int J Mol Med ; 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31985017

RESUMO

3,4­Dihydroxyacetophenone (DHAP) exerts therapeutic effects on cardiovascular disease and pulmonary heart disease. However, it is not utilized as a clinical drug due to its rapid metabolism, short­acting effect and low oral bioavailability. In the present study, three derivatives of DHAP, including 4­acetyl­1,2­phenylene dipropionate (APDP), 1­(3­hydroxy­4­phenoxy­phenyl)­ethanone (HPPE) and a polymer derivative, PEG­DHAP, were synthesized via the esterification or etherification of hydroxyls at C3 and C4, which are the prime metabolism sites of DHAP. The physicochemical properties, pharmacokinetic and antiplatelet aggregation activities of these derivatives were measured to determine whether they can improve the defects of DHAP. The results revealed that APDP and HPPE exhibited markedly lower water solubility and higher oil­water partition coefficients compared to DHAP. APDP rapidly transformed into DHAP in vivo and in vitro, indicating that there were no significant differences in the values of mean residence time in vivo [MRT (0­t)], half­life [t1/2], oral bioavailability and antiplatelet aggregation activity in vivo and in vitro between the two agents. HPPE partially released DHAP for a period of time following oral administration. PEG­DHAP contained 12.47% DHAP dispersed into nanoparticles with a mean particle size of 260.90 nm. This was administered in aqueous solution and was demonstrated to release DHAP slowly following oral administration. These two derivatives significantly prolonged the in vivo acting time and increased the oral bioavailability of DHAP: Following intragastric administration, their MRT (0­t) and t1/2 values were 3.55­11.47­ and 6.63­11.25­fold higher compared with those of DHAP, respectively. Additionally, their relative bioavailability was 394.79 and 331.88%, respectively, and they exhibited longer acting times of significant antiplatelet aggregation activity. The results of the present study may thus provide a reference for the development of DHAP as an oral drug. Furthermore, the results if this study may prove to be useful to researchers addressing the issue of the poor bioavailability of phenolic drugs.

6.
Phytochemistry ; 171: 112234, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31901735

RESUMO

A total of fifteen grayanane diterpenoid glucosides including eight undescribed ones, pierisjaponosides A-H, were isolated from the leaves of Pieris japonica (Thunb.) D. Don ex G. Don (Ericaceae). Their structures were established by extensive spectros copic techniques including HRESIMS and NMR, as well as chemical methods. The absolute configurations of pierisjaponosides A, B, and D were finally established by single-crystal X-ray diffraction with Cu Kα radiation. This is the first time to report the crystal structure of a 5,9-epoxygrayanane diterpenoid glucoside. Pierisjaponoside E represents the first example of a 9ß-hydroxygrayan-1(10)-ene diterpenoid. All the isolated grayanane diterpenoid glucosides were evaluated for their analgesic activities in the acetic acid-induced writhing models in mice, and showed significant analgesic effects. Pierisjaponosides A and C-H, micranthanoside A, pieroside A, and craiobiosides A and B displayed significant analgesic effects with the writhe inhibition rates over 50% at a dose of 5.0 mg/kg. Pierisjaponoside E exhibited significant analgesic activities with the percentage inhibitions of 81.7%, 70.4%, and 52.1% at the doses of 5.0, 1.0, and 0.2 mg/kg, respectively. The preliminary structure-activity relationships of grayanane diterpenoid glucosides as potent analgesics were discussed, giving some clues to design novel analgesics.

7.
Biochem Biophys Res Commun ; 523(2): 493-499, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-31894018

RESUMO

MicroRNAs have a vital effect on the differentiation of many types of progenitor cells. Recent studies have suggested that miR-17 plays an important role in the differentiation process of brain neural progenitor cells (NPC). Nevertheless, its detailed functions in regulating retinal progenitor cells (RPC) remain unclear. In our study, overexpression and knockdown of miR-17 were performed by transfecting RPC with mimics and inhibitors, respectively. Next, we investigated the role of miR-17 in RPC proliferation and differentiation by the following experiments: qPCR, CCK8, Edu staining, immunostaining and Western blot. The results revealed that miR-17 inhibited RPC proliferation but enhanced differentiation. Furthermore, according to a web-based database analysis, we identified charged multivesicular body protein 1A (CHMP1A) as a target gene. A dual luciferase reporter system showed that miR-17 specifically binds to the CHMP1A 3' untranslated region (UTR). Next, our data showed upregulation of miR-17 decreased CHMP1A protein level, causing reduced proliferation and enhanced differentiation of RPC. Downregulation of miR-17 led to enhanced CHMP1A protein expression, increased RPC proliferation and decreased differentiation. Taken together, our data provide a proven pathway by which miR-17 regulates RPC proliferation and differentiation by targeting CHMP1A.

8.
J Agric Food Chem ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-31986031

RESUMO

An antioxidant peptide derived from egg white, Asp-His-Thr-Lys-Glu (DHTKE), possesses specific amino acids related to zinc delivery. This study aimed to demonstrate the molecular basis of interactions between the egg white peptide (DHTKE) and zinc ions and investigate the effect of the DHTKE-Zn complex on zinc delivery through the gastrointestinal system. Approximately one DHTKE molecule can bind one zinc ion (n = 1.048 ± 0.085) through its carboxyl, amino, and imidazole nitrogen groups on Asp, His, and Glu. The formed DHTKE-Zn complex presented uniformly distributed globular particles with a particle size of 100-500 nm and underwent dissociation and re-chelation during gastrointestinal digestion. Moreover, the DHTKE peptide mostly remained stable, with a retention rate of 98.32% under gastrointestinal digestion, although one degradation product (DHTK) was identified by nanoscale liquid chromatography-electrospray ionization-tandem mass spectrometry in the gastrointestinal digests; the effectiveness of DHTKE-Zn digests on enhancing absorption of zinc was comparable to that of the initial complex.

9.
Food Chem ; 310: 125867, 2020 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-31767486

RESUMO

Phosphorylation could improve functional characteristics of proteins/peptides, and might be used in the functional improvement of herring egg peptides owing to their enriched phosphorylation sites. The present study aimed to study the effect of phosphorylation on calcium-binding ability of herring egg peptides, and investigate the conformational structure and intermolecular forces of herring egg phosphopeptides (HEPPs)-calcium complex. The HEPPs were found to be superior in calcium-binding activities, as compared to the non-phosphorylated variant. This finding might be attributed to the interaction between calcium ions and the introduced phosphate groups of HEPPs. Calcium favored the formation of ß-sheet structure on the HEPPs and induced structural folding, thus assembling into spherical nanoparticles. The conformation of HEPPs-Ca nanoparticles was formed and stabilized mainly by hydrophobic interaction, hydrogen bonds and electrostatic interaction.

10.
Transbound Emerg Dis ; 67(1): 149-158, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31433123

RESUMO

Malignant catarrhal fever (MCF) is a fatal lymphoproliferative disease that represents a serious problem in the deer-rearing industry. To better understand an MCF-like disease that has emerged in northern China since 2015, we investigated ten cases by documenting clinical and epidemiological data and analysing causative agents and histopathological changes. In addition, a retrospective screen for Macavirus DNA and a questionnaire-based survey were conducted. Epizootic MCF in Chinese sika deer herds has emerged with a low morbidity of 3.8% (95% CI: 2.5%-5.1%) and a high mortality of 93.2% (95% CI: 86.6%-99.9%). The disease course varied from 3 to 12 days. Aetiologically, OvHV-2 was predominant in the MCFV, accounting for most MCF cases (21/23). In contrast, only two CpHV-2 isolates were phylogenetically closely related to CpHV-2. Diarrhoea and nasal discharges were the most frequent manifestations, although clinical signs varied in some cases. Pathologically typical lesions of haemorrhage, necrosis and lymphoid cell infiltration were readily observed in a variety of organs. Vasculitis caused by vascular and perivascular lymphoid cell infiltration was common. The retrospective survey suggested a low positive rate (3/275) of MCFV DNA in peripheral blood lymphocytes (PBL). The questionnaire-based survey suggested the disease was neglected by local veterinarians, who did not acknowledge the risk of co-rearing deer with reservoir species. Collectively, the emerging epizootic MCF in Chinese sika deer herds remains neglected, emphasizing the urgency of initiating full-field diagnoses and control strategies.

11.
Women Birth ; 33(1): e67-e71, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30935772

RESUMO

BACKGROUND: Obstetricians' beliefs, attitudes, and clinical practices related to cesarean delivery on maternal request appears particularly important in the context of high cesarean section rate. However, few relative studies have been conducted. AIM: To examine Chinese obstetricians' attitudes, beliefs, and clinical practices with regard to cesarean delivery on maternal request, and to explore influencing factors associated with their practices of cesarean delivery on maternal request. METHODS: A cross-sectional design was used. Self-administered anonymous questionnaires were distributed to eligible obstetricians at the Congress of the Shanxi Society of Gynecology and Obstetrics as well as the Congress of the Hainan Society of Gynecology and Obstetrics. The overall response rate was 526/649 (81.05%). Multivariate logistic regression models were used to examine independent effects on obstetrician's clinical practices related to cesarean delivery on maternal request. FINDINGS: Obstetricians who agreed with pregnant women's decision to choose cesarean section directly and believed the benefits of this procedure outweigh the risks had higher odds of performing cesarean delivery on maternal request. In addition, measures to decrease cesarean section at hospitals were associated with reduced likelihood to perform cesarean delivery on maternal request. CONCLUSIONS: The present study showed a strong correlation between obstetricians' attitudes, beliefs, as well as interventions to decrease cesarean section at hospitals and their clinical practices of cesarean delivery on maternal request. Measures to enhance the training of obstetricians and reduce CS at hospitals are essential to decrease the overall cesarean section rate in China.

12.
Radiol Med ; 125(2): 165-176, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31605354

RESUMO

AIMS: The aim of the study was to predict and assess treatment response by histogram analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to patients with locally advanced esophageal squamous cell carcinoma receiving chemoradiotherapy (CRT). MATERIALS AND METHODS: Seventy-two patients with locally advanced esophageal squamous cell carcinoma who underwent DCE-MRI before and after chemoradiotherapy were enrolled and divided into the complete response (CR) group and the non-CR group based on RECIST. The histogram parameters (10th percentile, 90th percentile, median, mean, standard deviation, skewness, and kurtosis) of pre-CRT and post-CRT were compared using a paired Student's t test in the CR and non-CR groups, respectively. The histogram parameter differences between the CR and the non-CR groups were compared using an unpaired Student's t test. A receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic performance. RESULTS: The histogram parameters of Ktrans values were observed to have significantly decreased after chemoradiotherapy in the CR group. The CR responders showed significantly higher median, mean, and 10th and 90th percentile of pre-Ktrans values than those of the non-CR group. The histogram analysis indicated the decreased heterogeneity in the CR group after CRT. Esophageal cancer with higher pre-Ktrans and lower post-Ktrans values indicated a good treatment response to CRT. Pre-Ktrans-10th showed the best diagnostic performance in predicting the chemoradiotherapy response. CONCLUSIONS: The histogram parameters of Ktrans are useful in the assessment and prediction of the chemoradiotherapy response in patients with advanced esophageal squamous cell carcinoma. DCE-MRI could serve as an adjunctive imaging technique for treatment planning.

13.
Neurosci Lett ; 715: 134628, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31738951

RESUMO

Ethanol (EtOH) exposure causes alterations of motor coordination, balance, behavior, speech, and certain cognitive functions are considered to be caused partly by impairment of cerebellar circuits function and modulation of synaptic transmission. The cerebellar cortical molecular layer interneuron-Purkinje cell (MLI-PC) synapses are critical for various information integration and transmission, which are sensitive to acute and chronic EtOH exposure. The aim of this study is to investigate the effect of chronic ethanol exposure on the facial stimulation-evoked MLI-PC synaptic transmission in urethane-anesthetized mice, by electrophysiological recording and pharmacological methods. Under current-clamp recording conditions, air-puff stimulation of ipsilateral whisker pad evoked MLI-PC synaptic transmission, which expressed an inhibitory component (P1) followed by a pause of simple spike (SS) firing in cerebellar PCs. Chronic ethanol exposure did not change the latency of the facial stimulation-evoked responses in cerebellar PCs, but induced significant enhancement of the stimulation-evoked MLI-PC synaptic transmission, which expressed increases in amplitude of P1 and pause of SS firing. The amplitude of P1 and pause of SS in ethanol exposure group were significant higher than that in control group. Cerebellar surface application of nitric oxide synthesis (NOS) inhibitor, L-NNA (5 mM) significantly decreased the amplitude of P1 and the pause of SS firing in EtOH exposure group, but did no effect on control group. In contrast, cerebellar surface application of NO donor, SNAP (100 µM) significantly increased the amplitude of P1 and the pause of SS firing in control group, but not in EtOH exposure group. These results indicated that chronic EtOH exposure significantly facilitated the sensory-evoked MLI-PC synaptic transmission via NO signaling pathway in mouse cerebellar cortex.

14.
Peptides ; 123: 170181, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31689455

RESUMO

Previous studies suggested that endoplasmic reticulum (ER) stress induced-apoptosis promoted vascular calcification (VC). Interestingly, erythropoietin (EPO), an endogenous glycoprotein, exerts multiple tissue protective effects by inhibiting ER stress and apoptosis. We investigated the role and potential mechanism of EPO on VC in chronic kidney disease (CKD) rats and cultured vascular smooth muscle cells (VSMCs). The calcification model was established by subtotal nephrectomy in vivo or phosphate overload in vitro. The protein level of EPO receptor (EPOR) was increased in the calcified aortas of CKD rats. EPO prevented the reduction of VSMC phenotypic markers, and reversed the increased calcium content and calcium salt deposition in the aortas of CKD rats and cultured calcified VSMCs. The protein levels of activating transcription factor 4 (ATF4) and glucose-regulated protein 94 (GRP94) were upregulated in aortas and VSMCs under calcifying conditions, indicating ER stress activation. EPO treatment of CKD rats or calcified VSMCs downregulated the protein levels of ATF4 and GRP94. Furthermore, ER stress-mediated apoptosis, determined by the protein levels of CCAAT/enhancer-binding protein-homologous protein and cleaved caspase 12, was increased in tunicamycin or calcification media-treated VSMCs, but the increased effect was reversed in EPO-treated groups. The increased apoptotic cells in calcified VSMCs, as indicated by Hoechst staining and flow cytometry, were downregulated by the co-administration of EPO or 4-phenyl butyric acid. In conclusion, EPO might attenuate VC by inhibiting ER stress mediated apoptosis through EPOR signaling.

15.
J Nat Med ; 74(1): 269-274, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31493217

RESUMO

One novel neoligan glucoside, Ginkgoside B (1), and one new glucose ester, 6-O-(4-hydroxyhydrocinnamoyl)-D-glucopyranose (2), along with nine known compounds (3-11) were isolated from the ethanol extract of Ginkgo biloba leaves. Their structures were elucidated by combination of spectroscopic analyses and alkaline methanolysis. The absolute configuration of compound 1 was determined by single-crystal X-ray diffraction. All the isolated compounds were evaluated for their cytotoxicity activities, and compound 11 exhibited IC50 values of 36.20 and 58.95 µM against 5637 and HeLa cell lines, respectively.

17.
Chem Sci ; 10(38): 8850-8854, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31803459

RESUMO

Solid-liquid separation of similarly sized organic molecules utilizing sorbents offers the potential for new energy-efficient approaches to a number of important industrial separations such as xylenes (C8) separations. Research on selective C8 sorption has tended to focus upon rigid porous materials such as zeolites and MOFs but has revealed generally weak selectivity that is inconsistent across the range of C8 molecules. Nevertheless, there are a few recent examples of non-porous molecular materials that exhibit relatively high selectivity for p-xylene (pX) from pX/oX, approaching that of the current benchmark pX sorbent, the zeolite H/ZSM-5. Herein, we report that a L-shaped Ag(i) complex, AgLClO4 (M), which crystallizes as a non-porous molecular solid material, offering exceptional performance for pX selectivity across the range of C8 isomers with liquid extraction selectivity values of 24.0, 10.4 and 6.2 vs. oX, eB and mX, respectively. The pX selectivities over oX and eB are among the highest yet reported. Moreover, M also exhibits strong vapor extraction selectivity and can be regenerated by exposure to vacuum drying.

18.
J Nat Prod ; 82(12): 3330-3339, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31809052

RESUMO

Thirteen new grayanane diterpenoids (1-13) and 15 known analogues (14-28) were isolated from a leaf extract of Pieris japonica. Their structures were determined by spectrometric and spectroscopic methods, including HRESIMS, NMR, IR, and UV. The absolute configurations of 1, 3, 7-9, and 16 were defined by single-crystal X-ray diffraction analysis. 17-Hydroxygrayanotoxin XIX (1) represents the first example of a 17-hydroxygrayan-15(16)-ene diterpenoid. Diterpenoids 1-28 were evaluated for their antinociceptive activities, and 4, 9, 13, 21, and 26-28 displayed significant antinociceptive activities at a dose of 5.0 mg/kg (ip) in the HOAc-induced writhing test in mice. 17-Hydroxygrayanotoxin XIX (1) exhibited potent antinociceptive effects with writhe inhibition rates of 56.3% and 64.8% at doses of 0.04 and 0.2 mg/kg, respectively, which were almost equivalent to the positive control, morphine. Rhodomollein X (26) and rhodojaponin VI (27) showed more potent antinociceptive effects than morphine at doses of 0.04 and 0.2 mg/kg. A preliminary structure-activity relationship for the antinociceptive effects of diterpenoids 1-28 is discussed.

19.
Blood Purif ; : 1-9, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31851984

RESUMO

BACKGROUND: The prognostic value of serum time-averaged albumin (TA-Alb) and time-averaged globulin (TA-Glo) combination on the peritonitis in peritoneal dialysis (PD) patients is unknown. METHODS: The patients who started PD treatment between July 2013 and 2018 were included. Serum Alb and globulin (Glo) were tested at baseline and monthly during follow-up. TA-Alb and TA-Glo were calculated until first peritonitis occurred or the end of the study. PD patients were divided into 4 groups based on the medians of TA-Alb and TA-Glo separately. Cox regression was conducted to identify the hazard ratios (HRs) of peritonitis among categorical groups. RESULTS: Three hundred and sixty-three patients were included and among them 109 patients experienced first peritonitis. Peritonitis patients had lower baseline Alb, TA-Alb, and TA-Glo levels and ultrafiltration volume. Multivariate cox regression analysis revealed that TA-Alb, TA-Glo, and baseline Alb were significantly associated with first peritonitis. The highest HR existed in Group 1 with lower Alb and lower Glo (HR 4.57, 95% CI 2.36-8.87, p < 0.001) compared with Group 4 with higher Alb and higher Glo. CONCLUSION: Lower TA-Glo is an independent risk factor for the first peritonitis in PD patients. Combined with lower TA-Alb will increase the predictive effect than separate factor alone.

20.
Cell Rep ; 29(13): 4568-4582.e5, 2019 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-31875561

RESUMO

In vitro gametogenesis is the process of making germline cells from human pluripotent stem cells. The foundation of this model is the quality of the first progenitors called primordial germ cells (PGCs), which in vivo are specified during the peri-implantation window of human development. Here, we show that human PGC (hPGC) specification begins at day 12 post-fertilization. Using single-cell RNA sequencing of hPGC-like cells (hPGCLCs) differentiated from pluripotent stem cells, we discovered that hPGCLC specification involves resetting pluripotency toward a transitional state with shared characteristics between naive and primed pluripotency, followed by differentiation into lineage-primed TFAP2A+ progenitors. Applying the germline trajectory to TFAP2C mutants reveals that TFAP2C functions in the TFAP2A+ progenitors upstream of PRDM1 to regulate the expression of SOX17. This serves to protect hPGCLCs from crossing the Weismann's barrier to adopt somatic cell fates and, therefore, is an essential mechanism for successfully initiating in vitro gametogenesis.

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