Transcripts of repetitive DNA elements signal to block phagocytosis of hematopoietic stem cells.

Macrophages maintain hematopoietic stem cell (HSC) quality by assessing cell surface Calreticulin (Calr), an "eat-me" signal induced by reactive oxygen species (ROS). Using zebrafish genetics, we identified Beta-2-microglobulin (B2m) as a crucial "don't eat-me" signal on blood stem cells. A chemical screen revealed inducers of surface Calr that promoted HSC proliferation without triggering ROS or macrophage clearance. Whole-genome CRISPR-Cas9 screening showed that Toll-like receptor 3 (Tlr3) signaling regulated b2m expression. Targeting b2m or tlr3 reduced the HSC clonality. Elevated B2m levels correlated with high expression of repetitive element (RE) transcripts. Overall, our data suggest that RE-associated double-stranded RNA could interact with TLR3 to stimulate surface expression of B2m on hematopoietic stem and progenitor cells. These findings suggest that the balance of Calr and B2m regulates macrophage-HSC interactions and defines hematopoietic clonality.

Summary of the International Patient Safety Conference, June 28-29, 2019, Kathmandu, Nepal.

Globally, medical errors are associated with an estimated $42 billion in costs to healthcare systems. A variety of errors in the delivery of healthcare have been identified by the World Health Organization and it is believed that about 50% of all errors are preventable. Initiatives to improve patient safety are now garnering increased attention across a range of countries in all regions of the world. From June 28--29, 2019, the first International Patient Safety Conference (IPSC) was held in Kathmandu, Nepal and attended by over 200 healthcare professionals as well as hospital, government, and non-governmental organization leaders. During the conference, presentations describing the experience with errors in healthcare and solutions to minimize future occurrence of adverse events were presented. Examples of systems implemented to prevent future errors in patient care were also described. A key outcome of this conference was the initiation of conversations and communication among important stakeholders for patient safety. In addition, attendees and dignitaries in attendance all reaffirmed their commitment to furthering actions in hospitals and other healthcare facilities that focus on reducing the risk of harm to patients who receive care in the Nepali healthcare system. This conference provides an important springboard for the development of patient-centered strategies to improve patient safety across a range of patient care environments in public and private sector healthcare institutions.