Single-cell lineage capture across genomic modalities with CellTag-multi reveals fate-specific gene regulatory changes.

Complex gene regulatory mechanisms underlie differentiation and reprogramming. Contemporary single-cell lineage-tracing (scLT) methods use expressed, heritable DNA barcodes to combine cell lineage readout with single-cell transcriptomics. However, reliance on transcriptional profiling limits adaptation to other single-cell assays.

Single-cell lineage tracing reveals hierarchy and mechanism of adipocyte precursor maturation.

White adipose tissue is crucial in various physiological processes. In response to high caloric intake, adipose tissue may expand by generating new adipocytes. Adipocyte precursor cells (progenitors and preadipocytes) are essential for generating mature adipocytes, and single-cell RNA sequencing provides new means to identify these populations.

Dermal Adipocyte Lipolysis and Myofibroblast Conversion Are Required for Efficient Skin Repair.

Mature adipocytes store fatty acids and are a common component of tissue stroma. Adipocyte function in regulating bone marrow, skin, muscle, and mammary gland biology is emerging, but the role of adipocyte-derived lipids in tissue homeostasis and repair is poorly understood. Here, we identify an essential role for adipocyte lipolysis in regulating inflammation and repair after injury in skin.

Regulated in Development and DNA Damage Responses 1 Prevents Dermal Adipocyte Differentiation and Is Required for Hair Cycle-Dependent Dermal Adipose Expansion.

Dermal white adipose tissue (dWAT) expansion is associated with important homeostatic and pathologic processes in skin. Even though mTOR/protein kinase B signaling is important for adipogenesis, the role of regulated development of DNA damage responses 1 (REDD1), a negative regulator of mTOR/protein kinase B, is poorly understood. Loss of REDD1 in mice resulted in reduction of body mass, total fat, size of gonadal white adipose tissue, and interscapular brown adipose tissue.

Tracing the Origins of Axolotl Limb Regeneration.

The mechanisms underlying limb regeneration in axolotl have remained elusive due to limitations in isolating and tracking the cells that replenish lost tissues. In recent work, Elly Tanaka and Barbara Treutlein unite their expertise in axolotl limb regeneration and single-cell analysis to reveal cellular mechanisms underpinning regeneration.

Myofibroblast proliferation and heterogeneity are supported by macrophages during skin repair.

During tissue repair, myofibroblasts produce extracellular matrix (ECM) molecules for tissue resilience and strength. Altered ECM deposition can lead to tissue dysfunction and disease. Identification of distinct myofibroblast subsets is necessary to develop treatments for these disorders.

Skin Adipocyte Stem Cell Self-Renewal Is Regulated by a PDGFA/AKT-Signaling Axis.

Tissue growth and maintenance requires stem cell populations that self-renew, proliferate, and differentiate. Maintenance of white adipose tissue (WAT) requires the proliferation and differentiation of adipocyte stem cells (ASCs) to form postmitotic, lipid-filled mature adipocytes. Here we use the dynamic adipogenic program that occurs during hair growth to uncover an unrecognized regulator of ASC self-renewal and proliferation, PDGFA, which activates AKT signaling to drive and maintain the adipogenic program in the skin.

The Role of Adipocytes in Tissue Regeneration and Stem Cell Niches.

Classically, white adipose tissue (WAT) was considered an inert component of connective tissue but is now appreciated as a major regulator of metabolic physiology and endocrine homeostasis. Recent work defining how WAT develops and expands in vivo emphasizes the importance of specific locations of WAT or depots in metabolic regulation. Interestingly, mature white adipocytes are integrated into several tissues.

Arsenic-induced S phase cell cycle lengthening is associated with ROS generation, p53 signaling and CDC25A expression.

Cellular response to arsenic is strongly dependent on p53 functional status. Primarily arresting the cell cycle in G1 or G2/M phases, arsenic treatment also induces an increase in the S-phase time in wild-type p53 cells. In contrast, cells with a non-functional p53 display only a subtle increase in the S phase, indicating arsenic differentially affects the cell cycle depending on p53 status.

Adipocytes in skin health and disease.

Adipocytes are intimately associated with the dermal compartment of the skin, existing in a specialized dermal depot and displaying dynamic changes in size during tissue homeostasis. However, the roles of adipocytes in cutaneous biology and disease are not well understood. Traditionally, adipocytes within tissues were thought to act as reservoirs of energy, as thermal, or as structural support.

Retinoic acid and androgen receptors combine to achieve tissue specific control of human prostatic transglutaminase expression: a novel regulatory network with broader significance.

In the human prostate, expression of prostate-specific genes is known to be directly regulated by the androgen-induced stimulation of the androgen receptor (AR). However, less is known about the expression control of the prostate-restricted TGM4 (hTGP) gene. In the present study we demonstrate that the regulation of the hTGP gene depends mainly on retinoic acid (RA).

Baculoviruses as gene therapy vectors for human prostate cancer.

Prostate cancer is the most commonly diagnosed cancer in ageing men in the western world. While the primary cancers can be treated with androgen ablation, radiotherapy and surgery, recurrent castration resistant cancers have an extremely poor prognosis, hence promoting research that could lead to a better treatment. Targeted therapeutic gene therapy may provide an attractive option for these patients.