Abstract: Aims Macrophages have a critical and dual role in post-ischaemic cardiac repair, as they can foster both tissue healing and damage. Multiple subsets of tissue resident and monocyte-derived macrophages coexist in the infarcted heart, but their precise identity, temporal dynamics, and the mechanisms regulating their acquisition of discrete states are not fully understood. To address this, we used multi-modal single-cell immune profiling, combined with targeted cell depletion and macrophage fate mapping, to precisely map monocyte/macrophage transitions after experimental myocardial infarction. Methods and results We performed single-cell transcriptomic and cell-surface marker profiling of circulating and cardiac immune cells in mice challenged with acute myocardial infarction, and integrated single-cell transcriptomes obtained before and at 1, 3, 5, 7, and 11 days after infarction. Using complementary strategies of CCR2+ monocyte depletion and fate mapping of tissue resident macrophages, we determined the origin of cardiac macrophage populations. The macrophage landscape of the infarcted heart was dominated by monocyte-derived cells comprising two pro-inflammatory populations defined as Isg15hi and MHCII+Il1b+, alongside non-inflammatory Trem2hi cells. Trem2hi macrophages were observed in the ischaemic area, but not in the remote viable myocardium, and comprised two subpopulations sequentially populating the heart defined as Trem2hiSpp1hi monocyte-to-macrophage intermediates, and fully differentiated Trem2hiGdf15hi macrophages. Cardiac Trem2hi macrophages showed similarities to 'lipid-associated macrophages' found in mouse models of metabolic diseases and were observed in the human heart, indicating conserved features of this macrophage state across diseases and species. Ischaemic injury induced a shift of circulating Ly6Chi monocytes towards a Chil3hi state with granulocyte-like features, but the acquisition of the Trem2hi macrophage signature occurred in the ischaemic tissue. In vitro, macrophages acquired features of the Trem2hi signature following apoptotic-cell efferocytosis. Conclusion Our work provides a comprehensive map of monocyte/macrophage transitions in the ischaemic heart, constituting a valuable resource for further investigating how these cells may be harnessed and modulated to promote post-ischaemic heart repair

Nous présentons deux dispositifs microfluidiques, aussi appelés Laboratoires-sur-Puces, fondés sur deux technologies : la microfluidique et les billes magnétiques. Un premier laboratoire-sur-puce est dédié à la recherche de cellules tumorales circulantes. Les billes magnétiques sont auto-organisées sur un dépôt magnétique de ferrofluide obtenu par tamponnage moléculaire et les cellules sont séparées sur la base de protéines de membranes à leur surface. Les expériences menées établissent les performances de rendement et de pureté de la séparation cellulaire. On démontre que les cellules capturées peuvent être remises en culture. Comme validation clinique, ce système a été utilisé pour le typage de cellules tumorales circulantes lymphoïdes issues de leucémies et de lymphomes à l’aide de microscopie confocale à haute résolution. Un deuxième laboratoire-sur-puce a été utilisé pour la recherche de bactéries infectieuses. Un module de concentration d’ADN a été mis en place à l’aide de billes magnétiques organisées en réseau très dense de billes. L’ADN est retenu par sa charge sur les billes à faible pH et élué par augmentation de pH. La preuve de concept du système est apportée.