Project description:Patients who are diagnosed with thrombotic thrombocytopenic purpura (TTP) during pregnancy are at increased risk of maternal and fetal complications including fetal demise. We present a case of a 32-year-old G3P0 (gravida 3, para 0) who presented at 20 weeks’ gestation with a new diagnosis of congenital TTP (cTTP) and fetal demise. Methods: We describe the pathophysiology of pregnancy complications in a patient with cTTP using platelet procoagulant membrane dynamics analysis and quantitative proteomic studies, compared to 4 pregnant patients with gestational hypertension, 4 pregnant patients with preeclampsia and 4 healthy pregnant controls. Results: The cTTP patient had increased P-selectin, tissue factor expression, annexin-V binding on platelets and neutrophils, and localized thrombin generation, suggestive of hypercoagulability. Among 15 proteins that were upregulated, S100A8 and S100A9 were distinctly overexpressed.Conclusions: There is platelet-neutrophil activation and interaction, platelet hypercoagulability and proinflammation in our case of cTTP with fetal demise.
Project description:The functions of innate lymphoid cells (ILCs) in immune system are increasingly appreciated, whereas the early development of ILCs in human remains elusive. In this study, we sorted humanhematopoietic stem progenitor cells, lymphoid progenitors, presumed ILC progenitor/precursors and mature ILCs in the fetal hematopoietic, lymphoid and non-lymphoid tissues, from 8 to 12 PCW,for single-cell RNA-sequencing, followed by computational analysis and functional validation. We delineated the early phase of ILC development, from hematopoietic stem progenitor cells to multipotent lymphoid progenitors and to ILC progenitors, which mainly occurred in fetal liver and intestine. We further unveiled interleukin-3 receptor alpha (IL-3RA) as the surface marker for the lymphoid progenitors with T cell, B cell and ILC potentials. Notably, we determined the heterogeneity and tissue distribution of each ILC subpopulation, revealing the shared proliferating characteristics of the precursors of each ILC subtype. Additionally, a novel unconventional ILC2 subpopulation (CRTH2-CCR9+ ILC2) was identified in fetal thymus. Taken together, our study illuminates the precise cellular and molecular features underlying the stepwise formation of human fetal ILC hierarchy with remarkable spatiotemporal heterogeneity.
Project description:Innate lymphoid cells (ILC) in the small intestine govern immune homeostasis and protect the host against gut pathogens. While distinct cell-intrinsic signals have been identified that determine ILC development and differentiation, it has remained unclear which cell population regulates ILC sustenance. Using unbiased single cell RNA transcriptomic analysis of intestinal fibroblasts, we have identified a specialized Ccl19-expressing fibroblastic reticular cell (FRC) population that underpins solitary intestinal lymphoid tissue (SILT) structures including cryptopatches and isolated lymphoid follicles. Conditional ablation of lymphotoxin-β receptor (LTβR) signalling in SILT FRC impeded the maturation of isolated lymphoid follicles and blocked ILC maintenance through the downregulation of IL-7, consequently resulting in the elevated susceptibility to bacterial infection. Moreover, specific Ltbr ablation in FRC during adulthood revealed that constant LTβR-dependent FRC-ILC interaction is required to maintain SILT structures and ILC populations. Taken together, our study unveils a critical intestinal FRC niche that secures protective gut immunity.
Project description:We identified a new type of bone marrow progenitors termed early innate lymphoid cell progenitor (EILP) using TCF-1 GFP reporter mice. We compared the transcriptomes of early innate lymphoid cell progenitors (EILP) with other early progenitors, including HSC, LMPP, CMP, CLP, ETP and DN3.
Project description:Natural Killer (NK) cells at different developmental stages (common lymphoid progenitor (CLP), innate lymphoid cell progenitors (ILCP), and refined NK progenitor (NKP)) were collected from Vav1+iCre FOXO1,3flox/flox mice (C57BL/6 background). Total RNA was harvested and sequenced with a strand-specific paired-end RNA-seq protocol.
Project description:Diabetes is associated with increased risk of stillbirth and shoulder dystocia. Compared with uncomplicated pregnancies, diabetic patients have a 4-6x risk of stillbirth and 2-3x risk of shoulder dystocia. A 34?yo G2P0010 presented with a 40+3?wga IUFD with nonstandard antenatal glucose screening. Admission labs included a hemoglobin A1c of 6.6. She had a vaginal delivery complicated by a 30-minute shoulder dystocia that was not relieved by McRoberts, suprapubic pressure, Rubin II, Wood's Screw, or posterior arm delivery. Nitroglycerine was administered, after which Wood's Screw was successful resulting in delivery of an infant weighing 4190 grams (85th percentile for gestational age). A 31?yo G1 presented with a 37+1?wga IUFD. Her 28?wga three-hour GTT was notable for an elevated value at one hour (216?mg/dL). Admission labs included a hemoglobin A1c of 6.6. She had a vaginal delivery complicated by a 30-minute shoulder dystocia that was relieved via posterior axillary sling after failure of McRoberts, suprapubic pressure, Rubin II, Wood's Screw, and Gaskin's, resulting in the delivery of an infant weighing 3590?g (92nd percentile for gestational age). We present two cases of severe shoulder dystocia in patients who both presented with term IUFD and diabetic-range hemoglobin A1c. There is minimal literature on diabetic patients with pregnancies affected by both stillbirth and shoulder dystocia. These cases underscore the importance of glucose screening and control to prevent catastrophic obstetric outcomes.