Anatomical localization of progenitor cells in human breast tissue reveals enrichment of uncommitted cells within immature lobules

Introduction: Lineage tracing studies in mice have revealed the localization and existence of lineage-restricted mammary epithelial progenitor cells that functionally contribute to expansive growth during puberty and differentiation during pregnancy. However, extensive anatomical differences between mouse and human mammary tissues preclude the direct translation of rodent findings to the human breast. Therefore, here we characterize the mammary progenitor cell hierarchy and identify the anatomic location of progenitor cells within human breast tissues. Methods: Mammary epithelial cells (MECs) were isolated from disease-free reduction mammoplasty tissues and assayed for stem/progenitor activity in vitro and in vivo. MECs were sorted and evaluated for growth on collagen and expression of lineages markers. Breast lobules were microdissected and individually characterized based on lineage markers and steroid receptor expression to identify the anatomic location of progenitor cells. Spanning-tree progression analysis of density-normalized events (SPADE) was used to identify the cellular hierarchy of MECs within lobules from high-dimensional cytometry data. Results: Integrating multiple assays for progenitor activity, we identified the presence of luminal alveolar and basal ductal progenitors. Further, we show that Type I lobules of the human breast were the least mature, demonstrating an unrestricted pattern of expression of luminal and basal lineage markers. Consistent with this, SPADE analysis revealed that immature lobules were enriched for basal progenitor cells, while mature lobules consisted of increased hierarchal complexity of cells within the luminal lineages. Conclusions: These results reveal underlying differences in the human breast epithelial hierarchy and suggest that with increasing glandular maturity, the epithelial hierarchy also becomes more complex. Electronic supplementary material The online version of this article (doi:10.1186/s13058-014-0453-3) contains supplementary material, which is available to authorized users

Occupational Injuries Among Construction Workers by Age and Related Economic Loss: Findings From Ohio Workers' Compensation, USA: 2007–2017

Background: This study examined age-group differences in the rate, severity, and cost of injuries among construction workers to support evidence-based worker safety and health interventions in the construction industry. Methods: Ohio workers' compensation claims for construction workers were used to estimate claim rates and costs by age group. We analyzed claims data auto-coded into five event/exposure categories: transportation incidents; slips, trips, and falls (STFs); exposure to harmful substances and environments; contact with objects and equipment (COB); overexertion and bodily reaction. American Community Survey data were used to determine the percentage of workers in each age group. Results: From 2007–2017, among 72,416 accepted injury claims for ∼166,000 construction full-time equivalent (FTE) per year, nearly half were caused by COB, followed by STFs (20%) and overexertion (20%). Claim rates related to COB and exposure to harmful substances and environments were highest among those 18–24 years old, with claim rates of 313.5 and 25.9 per 10,000 FTE, respectively. STFs increased with age, with the highest claim rates for those 55–64 years old (94.2 claims per 10,000 FTE). Overexertion claim rates increased and then declined with age, with the highest claim rate for those 35–44 years old (87.3 per 10,000 FTE). While younger workers had higher injury rates, older workers had higher proportions of lost-time claims and higher costs per claim. The total cost per FTE was highest for those 45–54 years old ($1,122 per FTE). Conclusion: The variation in rates of injury types by age suggests that age-specific prevention strategies may be useful

The small GTPase Ral mediates SDF-1-induced migration of B cells and multiple myeloma cells

Chemokine-controlled migration plays a critical role in B-cell development, differentiation, and function, as well as in the pathogenesis of B-cell malignancies, including the plasma cell neoplasm multiple myeloma (MM). Here, we demonstrate that stimulation of B cells and MM cells with the chemokine stromal cell-derived factor-1 (SDF-1) induces strong migration and activation of the Ras-like GTPase Ral. Inhibition of Ral, by expression of the dominant negative RalN28 mutant or of RalBPDeltaGAP, a Ral effector mutant that sequesters active Ral, results in impaired SDF-1-induced migration of B cells and MM cells. Of the 2 Ral isoforms, RalA and RalB, RalB was found to mediate SDF-1-induced migration. We have recently shown that Btk, PLCgamma2, and Lyn/Syk mediate SDF-1-controlled B-cell migration; however, SDF-1-induced Ral activation is not affected in B cells deficient in these proteins. In addition, treatment with pharmacological inhibitors against PI3K and PLC or expression of dominant-negative Ras did not impair SDF-1-induced Ral activation. Taken together, these results reveal a novel function for Ral, that is, regulation of SDF-1-induced migration of B cells and MM cells, thereby providing new insights into the control of B-cell homeostasis, trafficking, and function, as well as into the pathogenesis of M