Volume 25 Issue 2, February 2023

Daylon James is an associate professor at Weill Cornell Medicine in New York, where his work focuses on reproductive biology and cell-based approaches for treating infertility. Arun Sharma is an assistant professor at the Cedars-Sinai Medical Center Regenerative Medicine Institute, and his lab works on modelling cardiovascular diseases and developing cell-based screening platforms for drug toxicity. Many of us also know them as the hosts of the Stem Cell Podcast. Here, we ask them about the podcast and discuss their view on the stem cell field and science communication.

Since stem cells were first discovered, researchers have identified distinct stem cell populations in different organs and with various functions, converging on the unique abilities of self-renewal and differentiation toward diverse cell types. These abilities make stem cells an incredibly promising tool in therapeutics and have turned stem cell biology into a fast-evolving field. Here, stem cell biologists express their view on the most striking advances and current challenges in their field.

Extramitochondrial coenzyme Q (CoQ) can function as a potent anti-ferroptosis radical trapper. However, it is largely unknown how CoQ is transported from mitochondria to the plasma membrane. A study now suggests that PARL-mediated STARD7 processing is responsible for the cellular distribution of CoQ.

Bivalent genes are regulated by a balance between repressive Polycomb group proteins and activating trithorax group proteins. A new study has revealed that MENIN, an accessory component of KMT2A/B methyltransferase complexes, has an unorthodox role in repressing bivalent genes, alongside Polycomb repressive complexes.

An ependymoma subtype is driven by fusion proteins related to the transcriptional regulator YAP1. Research now shows that localization of these fusion proteins within nuclear condensates is necessary and sufficient for tumour formation through the activation of various genetic and epigenetic oncogenic mechanisms.

Tight regulation of the activity of EWS–ETS fusion proteins is essential for the growth of Ewing sarcomas. Two new studies show that the transcriptional repressor ETV6 is essential for tumour growth, acting to restrain fusion-protein-mediated gene activation, and revealing the importance of tissue-specific transcription factors to oncogenesis.

Tumour-initiating cells are resistant to challenging growth conditions during the initiation of pancreatic cancer, but how transformed cells acquire a stress-resistant, tumour-initiating state remains unclear. Here, the authors identify a signalling cascade in which LPAR4 induces fibronectin production, cancer stemness and a tumour-initiating niche.

Contraction of the hair follicle-lining dermal sheath smooth muscle generates the forces necessary for the tissue remodelling that takes place during the regression phase of the hair growth cycle. This study reveals that endothelin signalling — from epithelial progenitors at the follicle bottleneck region to its neighbouring dermal sheath — is the main contraction-activating pathway.

Martino, Sunkara et al. report that endothelin produced by hair follicle progenitors binds to endothelin receptors on dermal sheath cells to trigger their contraction and hair follicle regression.

Daeden et al. report that branched Actin modulates size asymmetry in Drosophila sensory organ precursor cell division.

Deshwal et al. show that the protease PARL regulates coenzyme Q (CoQ) via the lipid transfer protein STARD7. Mitochondrial STARD7 ensures CoQ synthesis; cytosolic STARD7 preserves CoQ transport to the membrane, protecting cells against ferroptosis.

With whole-genome screens using a bivalent MHC class I gene expression readout, Sparbier et al. identify opposing roles for Menin and KMT2A/B in modulating activating H3K4me3 versus repressive H3K27me3 at bivalent promoters to regulate gene activation.

Liu et al. demonstrate that CK2 phosphorylates CLOCK to promote its nuclear exportation and cytosolic accumulation, thereby acetylating and stabilizing PRPS1/2 and enhancing de novo nucleotide synthesis to facilitate liver tumour growth.

Independent but complementary studies from Vakoc and Stegmaier identify and characterize a role for ETV6 in counteracting the transcriptional activity of EWS–FLI during Ewing sarcoma development, which may be targeted for therapeutic benefits.

Independent but complementary studies from Vakoc and Stegmaier identify and characterize a role for ETV6 in counteracting the transcriptional activity of EWS-FLI1 during Ewing sarcoma development, which may be targeted for therapeutic benefits.

Wu et al. identify a mechanistic role for LPAR4 in promoting a fibronectin-rich extracellular matrix via AKT, CREB and integrins, thereby generating a niche that facilitates initiation of pancreatic cancer.

Hu et al. report that patient-derived YAP fusion proteins undergo liquid–liquid phase separation in the nucleus to drive ependymoma tumourigenesis, altering transcription through transcription factor recruitment and alteration of genomic methylation.

Lotfollahi et al. present ExpiMap, a deep-learning model enabling interpretable reference mapping of RNA sequencing data using biologically defined entities, offering end-to-end analysis from dataset integration to functional interpretation.

Sountoulidis et al. provide a spatial gene expression atlas of human embryonic lung during the first trimester of gestation and identify 83 cell identities corresponding to stable cell types or transitional states.