Genetic lineage tracing identifies cardiac mesenchymal-to-adipose transition in an arrhythmogenic cardiomyopathy model

Arrhythmogenic cardiomyopathy(ACM)is one of the most common inherited cardiomyopathies,characterized by progressive fibrofatty replacement in the myocardium.However,the cellular origin of cardiac adipocytes in ACM remains largely unknown.Unraveling the cellular source of cardiac adipocytes in ACM would elucidate the underlying pathological process and provide a potential target for therapy.Herein,we generated an ACM mouse model by inactivating desmosomal gene desmoplakin in cardiomyocytes;and examined the adipogenic fates of several cell types in the disease model.The results showed that SOX9^(+),PDGFRa^(+),and PDGFRb^(+)mesenchymal cells,but not cardiomyocytes or smooth muscle cells,contribute to the intramyocardial adipocytes in the ACM model.Mechanistically,Bmp4 was highly expressed in the ACM mouse heart and functionally promoted cardiac mesenchymal-to-adipose transition in vitro.

Differences in the population of genetics of Mycobacterium tuberculosis between urban migrants and local residents in Beijing, China

Background Currently, migration has become one of the risk factors of high burden of tuberculosis in China. This study was to explore the influence of mass migration on the dynamics of Mycobacterium （M.） tuberculosis in Beijing, the capital and an urban area of China.

Embryonic lineage tracing with Procr-CreER marks balanced hematopoietic stem cell fate during entire mouse lifespan

The functional heterogeneity of hematopoietic stem cells(HSCs) has been comprehensively investigated by single-cell transplantation assay.However,the heterogeneity regarding their physiological contribution remains an open question,especially for those with life-long hematopoietic fate of rigorous selfrenewing and balanced differentiation capacities.In this study,we revealed that Procr expression was detected principally in phenotypical vascular endothelium co-expressing DII4 and CD44 in the midgestation mouse embryos,and could enrich all the HSCs of the embryonic day 11.5(E11.5) aortagonad-mesonephros(AGM) region.We then used a temporally restricted genetic tracing strategy to irreversibly label the Procr-exp res sing cells at E9.5.Interestingly,most labeled mature HSCs in multiple sites(such as AGM) around E11.5 were functionally categorized as lymphomyeloid-balanced HSCs assessed by direct transplantation.Furthermore,the labeled cells contributed to an average of 7.8% of immunophenotypically defined HSCs in E14.5 fetal liver(FL) and 6.9% of leukocytes in peripheral blood(PB) during one-year follow-up.Surprisingly,in aged mice of 24 months,the embryonically tagged cells displayed constant contribution to leukocytes with no bias to myeloid or lymphoid lineages.Altogether,we demonstrated,for the first time,the existence of a subtype of physiologically long-lived balanced HSCs as hypothesized,whose precise embryonic origin and molecular identity await further characterization.