Cells and gene expression programs in the adult human heart

Monika Litvinukova; Carlos Talavera-Lopez; Henrike Maatz; Daniel Reichart; Catherine L. Worth; Eric L. Lindberg; Masatoshi Kanda; Krzysztof Polanski; Eirini S. Fasouli; Sara Samari; Kenny Roberts; Elizabeth Tuck; Matthias Heinig; Daniel DeLaughter; Barbara McDonough; Hiroko Wakimoto; Joshua M. Gorham; Emily Nadelmann; Krishnaa T. Mahbubani; Kourosh Saeb-Parsy; Giannino Patone; Joseph J Boyle; Hongbo Zhang; Hao Zhang; Anissa Viveiros; Gavin Oudit; Omer Bayraktar; J. G. Seidman; Christine Seidman; Michela Noseda; Norbert Hubner; Sarah A. Teichmann

Cardiac EC are often under-studied due to their protruding nuclei, which may lead to damage during isolation. Indeed, in this study EC nuclei constituted 10.8% (atria) and 7.2% (ventricle) of cells, while immunohistochemistry data estimate that EC comprises >60% of non-myocytes in the heart 84 . By sequencing single cells and single nuclei from the same sample, we resolved seven populations including arterial, venous and lymphatic EC, and an atrial-enriched population. Using CellPhoneDB.org 85 A further cell compartment captured and analysed in depth were CD45+ immune cells. Due to their low frequency in tissues, the immune compartment is difficult to resolve using only nuclei. By performing CD45+ enrichment from the same cellular suspensions used for non-myocyte scRNA-Seq and using variational autoencoders, we identified 17 different immune cell populations across the myeloid and lymphoid lineages ( Figure 4A and 4B ). involvement. Here, we found that expression of the viral receptor ACE2 is higher in pericytes than in CM, as previously reported 87 , but also that neither pericytes nor CM express the protease that prime viral entry, TMPRSS2 . Instead CM and pericytes express CTSB and CTSL , which may also promote viral entry. ACE2 expression correlated with AGTR1