Biology subjects

McKinsey, G.

Publications and source records attributed to McKinsey, G..

2 recordsLinked to original sources

bioRxiv2023

Finding the right tool: a comprehensive evaluation of microglial inducible cre mouse models

The recent proliferation of new Cre and CreER recombinase lines provides researchers with a diverse toolkit to study microglial gene function. To determine how best to apply these lines in studies of microglial gene function, a thorough and detailed comparison of their properties is needed. Here, we examined four different microglial CreER lines (Cx3cr1CreER(Litt), Cx3cr1CreER(Jung), P2ry12CreER, Tmem119CreER), focusing on (1) recombination specificity; (2) leakiness - degree of non-tamoxifen recombination in microglia and other cells; (3) efficiency of tamoxifen-induced recombination; (4) extra-neural recombination -the degree of recombination in cells outside the CNS, particularly myelo/monocyte lineages (5) off-target effects in the context of neonatal brain development. We identify important caveats and strengths for these lines which will provide broad significance for researchers interested in performing conditional gene deletion in microglia. We also provide data emphasizing the potential of these lines for injury models that result in the recruitment of splenic immune cells.

neuroscience↗

bioRxiv2021

Single Cell Enhancer Activity Maps Neuronal Lineages in Embryonic Mouse Basal Ganglia

Enhancers integrate transcription factor signaling pathways that drive cell fate specification in the developing brain. We used single cell RNA-sequencing (scRNA-seq) to capture enhancer activity at single cell resolution and delineate specification of cells labeled by enhancers in mouse medial, lateral, and caudal ganglionic eminences (MGE, LGE, and CGE) at embryonic day (E)11.5. We combine enhancer-based reporter labeling with single-cell transcriptional readout to characterize enhancer activity and define cell populations in vivo. Seven enhancers had diverse activities in specific progenitor and neuronal populations within the GEs. We then applied enhancer-based labeling, scRNA-seq, and analysis of in situ hybridization (ISH) data to distinguish subtypes of MGE-derived GABAergic and cholinergic projection neurons and interneurons. This work demonstrates how the power of scRNA-seq can be extended by enhancer-based labelling and leveraging ISH data and reveals novel lineage specification paths underlying patterning of developing mouse brain.

neuroscience↗