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Generating stem cell-derived glucagon-producing α (SC-α cells) and insulin-producing β cells (SC-β cells) allows to engineer an in vitro biomimetic of the islet of Langerhans, the micro-organ controlling blood glucose, however, there is still a major knowledge gap in the mode and mechanism by which human SC-α and β cells are specified. Mouse studies postulated that Aristaless Related homeobox (Arx) and Paired box 4 (Pax4) transcription factors cross-inhibit each other in endocrine progenitors to promote α or β cell fate allocation, respectively. To test this model in human, we generated an ARXCFP/CFP; PAX4mCherry/mCherry double knock-in reporter induced pluripotent stem cell (iPSC) line to combine time-resolved cell lineage labeling with high-resolution single cell multiomic analysis. Strikingly, lineage labelling and tracing, proteomic and gene regulatory network (GRN) analysis and potency assays revealed a human specific mode and regulatory logic of α versus β cell fate allocation. Importantly, pharmacological perturbation using drugs previously proposed to trigger α-to-β cell transdifferentiation or identified via our GRN analysis led to enhanced endocrine induction and directed α vs β cell fate commitment. Thus, shedding light on basic mechanisms of endocrine induction and fate segregation not only paves the way to engineer islets from pluripotent stem cells, but also has broader implications for cell-replacement therapy, disease modelling and drug screening.

Background: Elderly hip fractures represent a global health care burden. Several reports expected a massive increase in the incidence of hip fractures by the next few decades. Knowing the epidemiology of hip fractures is crucial for planning health care policies. The purpose of this study is to provide a nationwide epidemiological overview of hip fractures in Jordan and to report the perioperative outcomes that may help to improve the delivered healthcare. . Methods: We conducted a retrospective study at 2 university hospitals and 2 major governmental hospitals in Jordan. We reviewed the records for all patients (age >55 years) who were diagnosed with hip fractures over a 3 years duration (2019-2021). We documented the patient's characteristics and the perioperative data (including preoperative, intraoperative, and postoperative details including the 1-year mortality). Results: The total number of included patients was 1268; more than half (53.7%) were females. The mean age is 75 years (SD 9.7). The most common fracture type was trochanteric (66.2%). 7% of patients had a prior contralateral hip fracture. The average time from admission to surgery was 2.96 days (SD 2.63). The surgery was done within 48 hours for 56.7% of patients. Approximately, one-third of all patients (34.5%) received a blood transfusion. The average length of hospital stay is 7.44 days (SD 5). The overall rate of postoperative thromboembolic events, readmission within 1 month, and revision for the same surgery are 2.4%, 10.7%, and 3% respectively. The 1-month, 6-month, and 12-month mortality rates are 4.5%, 9.1%, and 12.8% respectively. Conclusion: The annual incidence of elderly hip fractures in Jordan is approximately 96 per 100,000 individuals. The 1-year mortality rate of hip fractures in Jordan is 12.8%. Both findings are in the lower range of nearby Arab countries. Keywords: hip fracture, elderly, epidemiology, incidence, mortality, Jordan