ABSTRACT
Mast cells (MCs) are critical components of the innate immune system and important for host defense, allergy, autoimmunity, tissue regeneration and tumor progression. Dysregulated MC development leads to systemic mastocytosis (SM), a clinically variable but often devastating family of hematologic disorders. Here we report that induced expression of Lin28, a heterochronic gene and pluripotency factor implicated in driving a fetal hematopoietic program, caused MC accumulation in adult mice in target organs such as the skin and peritoneal cavity. In vitro assays revealed a skewing of myeloid commitment in LIN28B-expressing hematopoietic progenitors, with increased levels of LIN28B in common myeloid and basophil-MC progenitors altering gene expression patterns to favor cell fate choices that enhanced MC specification. In addition, LIN28B-induced MCs appeared phenotypically and functionally immature, and in vitro assays suggested a slowing of MC terminal differentiation in the context of LIN28B upregulation. Finally, interrogation of human MC leukemia samples revealed upregulation of LIN28B in abnormal MCs from patients with SM. This work identifies Lin28 as a novel regulator of innate immune function and a new protein of interest in MC disease.
Subject(s)
Cell Differentiation , DNA-Binding Proteins/physiology , Leukemia, Mast-Cell/pathology , Mast Cells/cytology , Mastocytosis, Systemic/pathology , Myeloid Cells/cytology , RNA-Binding Proteins/metabolism , Aged , Aged, 80 and over , Animals , Blotting, Western , Bone Marrow Transplantation , Cells, Cultured , Female , Flow Cytometry , Hematopoiesis/physiology , Humans , Leukemia, Mast-Cell/metabolism , Leukemia, Mast-Cell/therapy , Male , Mast Cells/metabolism , Mastocytosis, Systemic/metabolism , Mastocytosis, Systemic/therapy , Mice , Mice, Inbred C57BL , Mice, Knockout , Middle Aged , Myeloid Cells/metabolism , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain ReactionSubject(s)
Accidents, Occupational , Agriculture , Adolescent , Adult , Aged , Child , Child, Preschool , England , Female , Humans , Male , Middle Aged , Pilot ProjectsABSTRACT
An analysis of fertility and the provision of abortion and abortion-related services in the health districts of Wessex showed considerable variation between districts in the provision of formal family-planning services. The patterns of fertility varied between the districts and there appeared to be some relationship between family-planning provision and the rates for illegitimate and "legitimated" births and induced abortion. Although the region as a whole was meeting the demand of 42% of its abortion patients within the National Health Service, there was a considerable variation from district to district which could be explained only in part by variations in the provision of resources. The main differences could be accounted for by the attitudes of the women and of their general practitioners and consultants. Of Wessex women obtaining induced abortions privately at the British Pregnancy Advisory Service (B.P.A.S.) clinic at Brighton, 85% said they would have been willing to have an N.H.S. operation locally if one had been available but that no choice had been offered. It is concluded that the differences in provision between the health districts are more likely to be explained by the attitudes of doctors to providing this service than by the wishes of women to use private medical treatment.
Subject(s)
Abortion, Induced/supply & distribution , Family Planning Services , Health Services Accessibility , Regional Medical Programs/organization & administration , Abortion Applicants , Adolescent , Adult , Attitude of Health Personnel , Attitude to Health , England , Female , Humans , Illegitimacy , Marriage , Pregnancy , Pregnancy Trimester, First , Pregnancy Trimester, Second , Referral and ConsultationABSTRACT
Interviews with consultant gynaecologists serving the Wessex region about various aspects of their abortion work revealed considerable variations in attitudes and practice. Although the respondents referred to the same criteria in deciding whether to do an abortion, the assessments they made about the significance of these criteria were more of an individual matter. The variation in assessments partly explains the interdistrict disparities in the availability of N.H.S. abortions.
