Studies of human lung development have focused on epithelial and mesenchymal cell types and function, but much less is known about the developing lung immune cells, even though the airways are a ...major site of mucosal immunity after birth. An unanswered question is whether tissue-resident immune cells play a role in shaping the tissue as it develops in utero. Here, we profiled human embryonic and fetal lung immune cells using scRNA-seq, smFISH, and immunohistochemistry. At the embryonic stage, we observed an early wave of innate immune cells, including innate lymphoid cells, natural killer cells, myeloid cells, and lineage progenitors. By the canalicular stage, we detected naive T lymphocytes expressing high levels of cytotoxicity genes and the presence of mature B lymphocytes, including B-1 cells. Our analysis suggests that fetal lungs provide a niche for full B cell maturation. Given the presence and diversity of immune cells during development, we also investigated their possible effect on epithelial maturation. We found that IL-1β drives epithelial progenitor exit from self-renewal and differentiation to basal cells in vitro. In vivo, IL-1β-producing myeloid cells were found throughout the lung and adjacent to epithelial tips, suggesting that immune cells may direct human lung epithelial development.
Summary
S
treptomyces coelicolor
is a model for studying bacteria renowned as the foremost source of natural products used clinically. Post‐genomic studies have revealed complex patterns of gene ...expression and links to growth, morphological development and individual genes. However, the underlying regulation remains largely obscure, but undoubtedly involves steps after transcription initiation. Here we identify sites involved in
RNA
processing and degradation as well as transcription within a nucleotide‐resolution map of the transcriptional landscape. This was achieved by combining
RNA
‐sequencing approaches suited to the analysis of
GC
‐rich organisms.
E
scherichia coli
was analysed in parallel to validate the methodology and allow comparison. Previously, sites of
RNA
processing and degradation had not been mapped on a transcriptome‐wide scale for
E
. coli
. Through examples, we show the value of our approach and data sets. This includes the identification of new layers of transcriptional complexity associated with several key regulators of secondary metabolism and morphological development in
S
. coelicolor
and the identification of host‐encoded leaderless
mRNA
and
rRNA
processing associated with the generation of specialized ribosomes in
E
. coli
. New regulatory small
RNAs
were identified for both organisms. Overall the results illustrate the diversity in mechanisms used by different bacterial groups to facilitate and regulate gene expression.
We have investigated whether regions of the genome showing signs of positive selection in scans based on haplotype structure also show evidence of positive selection when sequence-based tests are ...applied, whether the target of selection can be localized more precisely, and whether such extra evidence can lead to increased biological insights. We used two tools: simulations under neutrality or selection, and experimental investigation of two regions identified by the HapMap2 project as putatively selected in human populations. Simulations suggested that neutral and selected regions should be readily distinguished and that it should be possible to localize the selected variant to within 40 kb at least half of the time. Re-sequencing of two ~300 kb regions (chr4:158Mb and chr10:22Mb) lacking known targets of selection in HapMap CHB individuals provided strong evidence for positive selection within each and suggested the micro-RNA gene hsa-miR-548c as the best candidate target in one region, and changes in regulation of the sperm protein gene
SPAG6
in the other.
We report a genome-wide scan for susceptibility loci to hypertension in a single Kyrgyz family where 10 of the affected relatives developed hypertension before the age of 35 years, and some members ...have suffered stroke. The early onset of disease and the geographic isolation of the Kyrgyz population are both expected to select for an increased influence of genetic factors in hypertension. We genotyped 44 individuals from this Krygyz family with 374 microsatellite markers, covering a 10-centimorgan map. Nonparametric analysis suggests that affected status is linked to loci in the chromosome 2q23 to q37 genomic interval, whereas 2-point parametric analysis returned a logarithm of odds score of 2.67 for marker D2S2330 (2q24.3). Multipoint linkage analysis substantiated the evidence for a hypertension susceptibility allele in the chromosome 2q23 to q36 region. Fine mapping and haplotype analysis implicate that the genetic lesion resides between markers D2S2380 (166.5 cM) and D2S335 (175.9 cM). This finding supports other recent studies of early onset hypertension suggesting that the region 2q24.3 to q31.1 encompasses a novel locus for premature hypertension.
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