Heterogeneous combinatorial expression of Hoxd genes in single cells during limb development.

BACKGROUND: Global analyses of gene expression during development reveal specific transcription patterns associated with the emergence of various cell types, tissues, and organs. These heterogeneous patterns are instrumental to ensure the proper formation of the different parts of our body, as shown by the phenotypic effects generated by functional genetic approaches. However, variations at the cellular level can be observed within each structure or organ. In the developing mammalian limbs, expression of Hox genes from the HoxD cluster is differentially controlled in space and time, in cells that will pattern the digits and the forearms. While the Hoxd genes broadly share a common regulatory landscape and large-scale analyses have suggested a homogenous Hox gene transcriptional program, it has not previously been clear whether Hoxd genes are expressed together at the same levels in the same cells. RESULTS: We report a high degree of heterogeneity in the expression of the Hoxd11 and Hoxd13 genes. We analyzed single-limb bud cell transcriptomes and show that Hox genes are expressed in specific combinations that appear to match particular cell types. In cells giving rise to digits, we find that the expression of the five relevant Hoxd genes (Hoxd9 to Hoxd13) is unbalanced, despite their control by known global enhancers. We also report that specific combinatorial expression follows a pseudo-time sequence, which is established based on the transcriptional diversity of limb progenitors. CONCLUSIONS: Our observations reveal the existence of distinct combinations of Hoxd genes at the single-cell level during limb development. In addition, we document that the increasing combinatorial expression of Hoxd genes in this developing structure is associated with specific transcriptional signatures and that these signatures illustrate a temporal progression in the differentiation of these cells.

Chromosomal contacts connect loci associated with autism, BMI and head circumference phenotypes.

Copy number variants (CNVs) are major contributors to genomic imbalance disorders. Phenotyping of 137 unrelated deletion and reciprocal duplication carriers of the distal 16p11.2 220 kb BP2-BP3 interval showed that these rearrangements are associated with autism spectrum disorders and mirror phenotypes of obesity/underweight and macrocephaly/microcephaly. Such phenotypes were previously associated with rearrangements of the non-overlapping proximal 16p11.2 600 kb BP4-BP5 interval. These two CNV-prone regions at 16p11.2 are reciprocally engaged in complex chromatin looping, as successfully confirmed by 4C-seq, fluorescence in situ hybridization and Hi-C, as well as coordinated expression and regulation of encompassed genes. We observed that genes differentially expressed in 16p11.2 BP4-BP5 CNV carriers are concomitantly modified in their chromatin interactions, suggesting that disruption of chromatin interplays could participate in the observed phenotypes. We also identified cis- and trans-acting chromatin contacts to other genomic regions previously associated with analogous phenotypes. For example, we uncovered that individuals with reciprocal rearrangements of the trans-contacted 2p15 locus similarly display mirror phenotypes on head circumference and weight. Our results indicate that chromosomal contacts' maps could uncover functionally and clinically related genes.

[Patients' satisfaction and waiting time in oncology day care centers in Champagne-Ardenne]. / Programme d'évaluation de l'administration des chimiothérapies en hôpital de jour en Champagne-Ardenne (PEACH) : satisfaction et délais d'attente des patients.

AIM: Quality of life of patients suffering from cancer may be influenced by the way healthcare is organized and by patient experiences. Nowadays, chemotherapy is often provided in day care centers. This study aimed to assess patient waiting time and satisfaction in oncology day care centers in Champagne-Ardenne, France. METHODS: This cross-sectional survey involved all patients receiving ambulatory chemotherapy during a one-week period in day care centers of Champagne-Ardenne public and private healthcare institutions participating in the study. Sociodemographic, medical and outpatient data were collected. Patient satisfaction was measured using the Out-Patsat35 questionnaire. RESULTS: Eleven (out of 16) oncology day care centers and 441 patients participated in the study. Most of the patients were women (n=252, 57.1%) and the mean age was 61±12 years. The mean satisfaction score was 82±14 (out of 100) and the mean waiting time between the assigned appointment time and administration of chemotherapy was 97±60 min. CONCLUSION: This study has shown that waiting times are important. However, patients are satisfied with the healthcare organization, especially regarding nursing support. Early preparation of chemotherapy could improve these parameters.

[What vascular events suggest a myeloproliferative disorder?]. / Devant quelles manifestations vasculaires rechercher un syndrome myéloprolifératif?

Patients with polycethemia vera (PV) or essential thrombocythemia (ET) are at increased risk of arterial and venous thromboembolic events. Arterial ischemic complications occur in 24 to 43% of these patients, particularly those with cardiovascular risk factors (especially cigarette smoking). Non-atheromatous arterial thrombosis concerns all large and medium-sized vessels, particularly cerebral, limb, coronary and digestive arteries. Extensive complications have been described in patients with lower limb occlusive arteriopathy, particularly stent or bypass thrombosis, critical ischemia. Juvenile myocardial infarction or rapid postangioplasty coronary thrombosis may reveal certain myeloproliferative disorders, particularly ET. Venous thrombosis is more frequent in PV than in ET; superficial or deep venous thromboses are seen. Thromboembolic events occur in about 25-30% of the patients and account for one-third of the deaths. Mesenteric vein thrombosis, portal thrombosis, or suprahepatic vein thrombosis may occur in all myeloproliferative disorders, but the pathogenesis is not fully understood. Pulmonary hypertension may be the consequence of local thrombosis in the pulmonary vasculature or may be due to the high blood flow in the right heart cavities. Microvascular circulatory disturbance includes erythromelalgia, Raynaud's phenomenon, digital ischemia, acrocyanosis, blue toe syndrome, livedo reticularis, cutaneous ulcers or necrotic purpura. All these manifestations may precede the myeloproliferative disorder by several months.

Follow-up of children born of bromocriptine-treated mothers.

A survey carried out in France at the beginning of 1984 concerning development of children born of mothers treated with bromocriptine (BC) during part or all of the pregnancy showed the absence of any adverse effects of BC in 64 children born from 53 mothers. In 60 cases, BC was prescribed (2.5-7.5 mg/day) for hyperprolactinemia; 23 mothers were treated with BC for 4 weeks or less, and 23 others for 30 weeks or more. After a follow-up of between 6 months and 9 years, all children are normal. Psychological development in the 23 children born to mothers treated with BC during more than 30 weeks of pregnancy actually appears more precocious, with excellent scholastic performance in the oldest.