Biology subjects

Rands, C. M.

Publications and source records attributed to Rands, C. M..

5 recordsLinked to original sources

bioRxiv2021

TRIM28-dependent SUMOylation protects the adult ovary from the male pathway

Gonadal sexual fate in mammals is determined during embryonic development and must be actively maintained in adulthood. In the mouse ovary, oestrogen receptors and FOXL2 protect ovarian granulosa cells from transdifferentiation into Sertoli cells, their testicular counterpart. However, the mechanism underlying their protective effect is unknown. Here, we show that TRIM28 is required to prevent female-to-male sex reversal of the mouse ovary after birth. We found that upon loss of Trim28, ovarian granulosa cells transdifferentiate to Sertoli cells through an intermediate cell type, different from gonadal embryonic progenitors. TRIM28 is recruited on chromatin in the proximity of FOXL2 to maintain the ovarian pathway and to repress testicular-specific genes. The role of TRIM28 in ovarian maintenance depends on its E3-SUMO ligase activity that regulates the sex-specific SUMOylation profile of ovarian-specific genes. Our study identifies TRIM28 as a key factor in protecting the adult ovary from the testicular pathway.

developmental biology↗

bioRxiv2020

Expression of Wnt5a defines the major progenitors of fetal and adult Leydig cells

Leydig cells (LCs) are the major androgen-producing cells in the testes. They arise from steroidogenic progenitors, whose origins, maintenance and differentiation dynamics remain largely unknown. Here, we identified Wnt5a as a specific marker of steroidogenic progenitors, whose expression begins at around E11.5-E12.5 in interstitial cells of the fetal mouse testis. In vivo lineage tracing indicates that Wnt5a-expressing progenitors are initially present in large numbers in the fetal testis and then progressively decrease as development progresses. We provide evidence that Wnt5a-expressing cells are bona fide progenitors of peritubular myoid cells as well as fetal and adult LCs, contributing to most of the LCs present in the fetal and adult testis. Additionally, we show in the adult testis that Wnt5a expression is restricted to a subset of LCs exhibiting a slow but noticeable clonal expansion, revealing hitherto unappreciated proliferation of fully differentiated LCs as a contribution to the adult LC pool.

developmental biology↗

bioRxiv2019

Phigaro: high throughput prophage sequence annotation

SummaryPhigaro is a standalone command-line application that is able to detect prophage regions taking raw genome and metagenome assemblies as an input. It also produces dynamic annotated \"prophage genome maps\" and marks possible transposon insertion spots inside prophages. It provides putative taxonomic annotations that can distinguish tailed from non-tailed phages. It is applicable for mining prophage regions from large metagenomic datasets.\n\nAvailabilitySource code for Phigaro is freely available for download at https://github.com/bobeobibo/phigaro along with test data. The code is written in Python.

bioinformatics↗

bioRxiv2019

Comparative genomics groups phages of Negativicutes and classical Firmicutes despite different Gram-staining properties

Negativicutes are Gram-Negative bacteria characterized by two cell membranes, but they are phylogenetically a side-branch of Gram-Positive Firmicutes that contain only a single membrane. We asked whether viruses (phages) infecting Negativicutes were horizontally acquired from Gram-Negative Proteobacteria, given the shared outer cell structure of their bacterial hosts, or if Negativicute phages co-evolved vertically with their hosts and thus resemble Gram-Positive Firmicute prophages. We predicted and characterised 485 prophages from Gram-Negative Firmicute genomes plus 2,977 prophages from other bacterial clades, and we used virome sequence data from 183 human stool samples to provide independent evidence for our predictions. The majority of the identified Negativicute prophages were lambdoids closer related to prophages from other Firmicutes than Proteobacteria by sequence relationship and genome organization (position of the lysis module). Only a single Mu-like candidate prophage and no clear P2-like prophages were identified in Negativicutes, both commonly found in Proteobacteria. Therefore, it is unlikely that Negativicute phages were acquired from Proteobacteria. Sequence-related prophages were identified in two distinct Negativicute orders (Veillonellales and Acidaminococcales) possibly suggesting horizontal cross-order phage infection between human gut commensals. Phages infecting these Negativicute orders occasionally harboured putative antibiotic resistance genes.

microbiology↗

bioRxiv2017

ACI-1 class A beta-lactamase is widespread across human gut microbiomes due to transposons harboured by tailed prophages

Antibiotic resistance is increasing among pathogens at unprecedented rates and the human body contains a large pool of antibiotic resistance genes that can be spread among bacteria by mobile genetic elements. Acidaminococcus intestini, a bacterium found in the human gut that belongs to the class of Negativicutes, is the first gram-negative coccus shown to be resistant to beta-lactam antibiotics. Resistance is conferred by aci1, a gene encoding the ACI-1 class A beta-lactamase, but the evolutionary history of aci1 and its distribution across other Negativicutes and in the human gut microbiota remains obscure. We discovered that ACI-1 proteins are phylogenetically distinct from class A beta-lactamases of gram-positive Firmicutes and that the aci1 gene occurs in bacteria scattered across the Negativicutes clade, suggesting possible mobilization. In the reference A. intestini RyC-MR95 strain, we found that aci1 is surrounded by mobile DNA, transposon derived sequences directly flank aci1 and are likely the vehicle for its mobility. These transposon sequences reside within a prophage context consisting of two likely degraded tailed prophages, the first prophages to be characterised in A. intestini. We found aci1 in at least 56 (4.4%) out of 1,267 human gut metagenome samples, mostly hosted within A. intestini, and, where could be determined, mostly within a similar constellation of mobile elements to that found in the reference A. intestini genome. These human samples are from individuals in Europe, China and the USA, showing that aci1 is widely distributed globally. Additionally, we examined the nine different Negativicute genome assemblies that contain aci1, and found that only two of these strains show a similar mobile element context around aci1 to the reference A. intestini with transposons adjacent to a tailed prophage. However, in all nine cases aci1 is flanked by transposon derived sequences, and these sequences are diverse, suggesting the activity and degradation of multiple transposons. Overall, we show that ACI-1 proteins form a distinct class A beta lactamase family, and that the aci1 gene is present in human guts worldwide within Negativicute bacterial hosts, due to transposons, sometimes inserted into tailed prophages.

microbiology↗