Dedifferentiation maintains melanocyte stem cells in a dynamic niche.

For unknow reasons, the melanocyte stem cell (McSC) system fails earlier than other adult stem cell populations1, which leads to hair greying in most humans and mice2,3. Current dogma states that McSCs are reserved in an undifferentiated state in the hair follicle niche, physically segregated from differentiated progeny that migrate away following cues of regenerative stimuli4-8. Here we show that most McSCs toggle between transit-amplifying and stem cell states for both self-renewal and generation of mature progeny, a mechanism fundamentally distinct from those of other self-renewing systems. Live imaging and single-cell RNA sequencing revealed that McSCs are mobile, translocating between hair follicle stem cell and transit-amplifying compartments where they reversibly enter distinct differentiation states governed by local microenvironmental cues (for example, WNT). Long-term lineage tracing demonstrated that the McSC system is maintained by reverted McSCs rather than by reserved stem cells inherently exempt from reversible changes. During ageing, there is accumulation of stranded McSCs that do not contribute to the regeneration of melanocyte progeny. These results identify a new model whereby dedifferentiation is integral to homeostatic stem cell maintenance and suggest that modulating McSC mobility may represent a new approach for the prevention of hair greying.

Piloting a prenatal care smartphone application and care navigation intervention at a federally qualified health center.

BACKGROUND: Given that smartphones are widely used among reproductive-age people of all socioeconomic backgrounds, a smartphone application may be a useful supplement to routine prenatal care. OBJECTIVE: This study aimed to describe the implementation of a smartphone app that offers patient education, depression screening, social determinants of health screening, and care coordination as an adjunct to routine prenatal care at a federally qualified health center. We further sought to characterize app engagement and the association of app use with pregnancy outcomes. STUDY DESIGN: The implementation of the smartphone app was a quality improvement initiative in which the app was made available to all people receiving prenatal care at a designated federally qualified health center between December 2020 and December 2021. Individuals who both initiated prenatal care at this site before 28 weeks of gestation and delivered at our institution during the above-defined period were studied retrospectively after obtaining institutional approval. Summary statistics were used to describe app implementation and information regarding social determinants of health and depression screening. Demographics and maternal and neonatal outcomes were compared between app enrollees and patients receiving prenatal care at the same site who were not enrolled in the app. Data were analyzed using the 2-sample t test to compare continuous variables and the chi-square test to compare categorical variables. RESULTS: Overall, 800 patients receiving prenatal care at the federally qualified health center during the identified period were telephonically approached for enrollment in the smartphone app. A total of 613 people (76.6%) were successfully reached, and of those successfully reached, 538 (87.7%) accepted enrollment in the app; 76.6% of app enrollees (n=412) completed at least 1 social determinants of health screen. Of those, 29.1% (n=120) screened positive for at least 1 need. Of those with positive screens, 51.7% (n=62) accepted referral to resources to address the identified need. Furthermore, 81% of app enrollees (n=443) completed at least 1 depression screen. Of those, 13.1% (n=58) screened positive for depression, and 37.9% (n=22) of those with positive screens accepted a referral to behavioral health services. A total of 483 people met the inclusion criteria for retrospective review: 264 were enrolled in the smartphone app and 219 were not. App enrollees were more likely to speak English (79.9% of app group vs 61.6% of the non-app group; P<.0001), identify as Hispanic (52.7% vs 39.7%; P=.02), and be privately insured (24.6% vs 15.5%; P=.005), and less likely to have a social determinants of health-related need (10.0% vs 21.0%; P=.01). There were no significant differences in mode of delivery or maternal and neonatal outcomes between the 2 groups. CONCLUSION: A high proportion of patients receiving care through our federally qualified health center enrolled in and used the smartphone app and its associated care coordination. This could be a useful tool to screen for depression and adverse social determinants of health in underserved communities. Given that individuals of higher-resource backgrounds seem more likely to enroll in smartphone apps, a more targeted approach is needed to help connect patients of lower-resource backgrounds to smartphone apps and the resources that they offer.