Biology subjects

Collin, M.

Publications and source records attributed to Collin, M..

3 recordsLinked to original sources

bioRxiv2019

A rule-based data-informed cellular consensus map of the human mononuclear phagocyte cell space

Single-cell genomic techniques are opening new avenues to understand the basic units of life. Large international efforts, such as those to derive a Human Cell Atlas, are driving progress in this area; here, cellular map generation is key. To expedite the inevitable iterations of these underlying maps, we have developed a rule-based data-informed approach to build next generation cellular consensus maps. Using the human dendritic-cell and monocyte compartment in peripheral blood as an example, we performed computational integration of previous, partially overlapping maps using an approach we termed backmapping, combined with multi-color flow-cytometry and index sorting-based single-cell RNA-sequencing. Our general strategy can be applied to any atlas generation for humans and other species.\n\nGraphical Abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=110 SRC=\"FIGDIR/small/658179v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (18K):\norg.highwire.dtl.DTLVardef@c1b7b2org.highwire.dtl.DTLVardef@32b68org.highwire.dtl.DTLVardef@16e5fcorg.highwire.dtl.DTLVardef@1552028_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIDefining a consensus of the human myeloid cell compartment in peripheral blood\nC_LIO_LI3 monocytes subsets, pDC, cDC1, DC2, DC3 and precursor DC make up the compartment\nC_LIO_LIDistinguish myeloid cell compartment from other cell spaces, e.g. the NK cell space\nC_LIO_LIProviding a generalizable method for building consensus maps for the life sciences\nC_LI

immunology↗

bioRxiv2019

Serum Flt3 ligand is a biomarker of progenitor cell mass and prognosis in acute myeloid leukemia

Fms-like tyrosine kinase 3 (Flt3) is a hematopoietic growth factor receptor expressed on lymphomyeloid progenitors and frequently, by AML blasts. Its ligand, Flt3L, has non-hematopoietic and lymphoid origins, is detectable during homeostasis and increases to high levels in states of hypoplasia due to genetic defects or treatment with cytoreductive agents. Measurement of Flt3L by ELISA reveals that Flt3+AML, is associated with depletion of Flt3L to undetectable levels. After induction chemotherapy, Flt3L is restored in patients entering CR, but remains depressed in those with refractory disease. Weekly sampling reveals marked differences in the kinetics of Flt3L response during the first 6 weeks of treatment, proportionate to the clearance of blasts and cellularity of the BM. In the UK NCRI AML17 trial, Flt3L was measured at day 26 in a subgroup of 135 patients with Flt3 mutation randomized to the tyrosine kinase inhibitor lestaurtinib. In these patients, attainment of CR was associated with higher Flt3L at day 26 (Mann-Whitney p < 0.0001). Day 26 Flt3L was also associated with survival: Flt3L [≤] 291pg/ml was associated with inferior event-free survival; and, Flt3L >1185pg/ml was associated with higher overall survival (p = 0.0119). Serial measurement of Flt3L in patients who had received a hematopoietic stem cell transplant for AML further illustrated the potential value of declining Flt3L to identify relapse. Together these observations suggest that measurement of Flt3L provides a non-invasive estimate of progenitor cell mass in most patients with AML, with the potential to inform clinical decisions.\n\nGraphical abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=151 HEIGHT=200 SRC=\"FIGDIR/small/588319_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (21K):\norg.highwire.dtl.DTLVardef@132f3f3org.highwire.dtl.DTLVardef@2e033eorg.highwire.dtl.DTLVardef@d70598org.highwire.dtl.DTLVardef@b0648a_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2019

Sweet revenge - Streptococcus pyogenes showcases first example of immune evasion through specific IgG glycan hydrolysis

Streptococcus pyogenes (Group A streptococcus, GAS) is an important human pathogen responsible for a wide variety of diseases from uncomplicated tonsillitis to life-threatening invasive infections. GAS secretes EndoS, an endoglycosidase able to specifically cleave the conserved N-glycan on human IgG antibodies. In vitro, removal of this glycan impairs IgG effector functions but its relevance to GAS infection in vivo is unclear. Using targeted mass spectrometry, we were able to characterize the effects of EndoS on host IgG glycosylation during the course of natural infections in human patients. We found substantial IgG glycan hydrolysis locally at site of infection as well as systemically in the most severe cases. Using these findings we were able to set up appropriate model systems to demonstrate decreased resistance to phagocytic killing of GAS lacking EndoS in vitro, as well as decreased virulence in a mouse model of invasive infection. This study represents the first described example of specific bacterial IgG glycan hydrolysis during infection and highlights the importance of IgG glycan hydrolysis for streptococcal pathogenesis. We thereby offer new insights into the mechanism of immune evasion employed by this pathogen with clear implications for treatment of severe GAS infections and future efforts at vaccine development.

microbiology↗