Metabolic health depends on the capacity of adipose tissue progenitor cells to undergo de novo adipogenesis. The cellular hierarchy and mechanisms governing adipocyte progenitor differentiation are incompletely understood. Through single-cell RNA sequence analyses, we show that the lineage hierarchy of adipocyte progenitors consists of distinct mesenchymal cell types that are present in both mouse and human adipose tissues. Cells marked by dipeptidyl peptidase–4 (DPP4)/CD26 expression are highly proliferative, multipotent progenitors. During the development of subcutaneous adipose tissue in mice, these progenitor cells give rise to intercellular adhesion molecule–1 (ICAM1)/CD54–expressing (CD54+) committed preadipocytes and a related adipogenic cell population marked by Clec11a and F3/CD142 expression. Transforming growth factor–β maintains DPP4+ cell identity and inhibits adipogenic commitment of DPP4+ and CD142+ cells. Notably, DPP4+ progenitors reside in the reticular interstitium, a recently appreciated fluid-filled space within and between tissues, including adipose depots.

4 Therapeutic.

Previous studies have demonstrated expression of epidermal growth factor receptors (EGFRs) in human cerebral meningiomas. However, the activation status of the EGFRs and whether they activate cytoplasmic mitogenic signaling pathways are not known. In this study, using Northern blot analysis and the polymerase chain reaction, the authors report expression of epidermal growth factor, transforming growth factor-alpha, and EGFR messenger RNA in 27 meningioma specimens. Using Western blot and immunohistochemical analyses of the meningioma samples, the authors demonstrate that the EGFRs expressed by these meningiomas are activated. These activated EGFRs interact with and phosphorylate Shc, an SH2 domain-containing adapter protein that is important in transducing mitogenic signals from EGFRs to the nucleus via activation of the Ras signaling pathway. These results support the concept that activation of EGFRs in human meningiomas by autocrine/paracrine stimulation may contribute to their proliferation.

X chromosome inactivation is the silencing mechanism eutherian mammals use to equalize the expression of X-linked genes between males and females early in embryonic development. In the mouse, genetic control of inactivation requires elements within the X inactivation center (Xic) on the X chromosome that influence the choice of which X chromosome is to be inactivated in individual cells. It has long been posited that unidentified autosomal factors are essential to the process. We have used chemical mutagenesis in the mouse to identify specific factors involved in X inactivation and report two genetically distinct autosomal mutations with dominant effects on X chromosome choice early in embryogenesis.