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Here the authors unveil the essential role of MCL-1 for adult hair follicle regeneration and inhibition of proliferation stress-induced apoptosis in mice. They also identify a P53/MCL-1/BAK axis balancing proliferation and death of activated hair follicle stem cells to ensure proper hair growth.

Intestinal crypt-resident Acinetobacter radioresistens secretes indole acetic acid which activates an Ahr-Wnt-β-catenin-EphB2 signalling axis to promote intestinal stem cell homeostasis and prevent tumour initiation and colorectal cancer.

Psoriasis is a partially heritable skin disorder, the genetic basis of which is not fully understood. Here, the authors use genome-wide association meta-analysis to discover psoriasis susceptibility loci and genes, which encode existing and potential new drug targets.

The Lgr5 (also known as Gpr49) gene is identified as a unique, single marker gene for adult stem cells and provides the first lineage tracing data for long-lived pluripotent stem cells in the small intestine and colon. These findings will have great impact on stem cell and cancer research.

Oncofetal (OnF) reprogramming, driven by YAP and AP-1, induces phenotypic plasticity and therapy resistance in WNT-dependent colorectal cancer (CRC). Targeting the OnF state in combination with chemotherapy substantially attenuates tumor growth in mouse models and patient-derived CRC tumoroids.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

The role of Lgr5+ cells in esophageal development has been unclear. Here, authors identify Lgr5+ cells in the developing mouse esophagus and reveal their crucial role in epithelial and muscle development.

Intestinal tumours can originate from Lgr5⁺ intestinal stem cells after genetic activation of the Wnt signalling pathway.

The ovary surface epithelium undergoes ovulation-induced tear and remodelling. Barker and colleagues have identified Lgr5-expressing stem cells in the mouse ovary and show that they contribute to ovary organogenesis as well as participate in epithelial repair throughout life.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Nature Biotechnology asks a selection of researchers about the most exciting frontier in their field and the most needed technologies for advancing knowledge and applications.

Biomarkers to indicate potential response to biologic therapeutics are needed for patients with psoriasis. Here the authors show that phosphorylation of NFκBp65 in cDC2 before therapy is an indication of non-response to the anti-TNF therapy adalimumab in patients with psoriasis.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

Barker and colleagues discuss the interplay between circadian rhythm, the tumor microenvironment and stem cells and how these are linked to metastasis as well as how these interactions could be clinically relevant.

Rune Toftgård and colleagues report that Lgr5, a G protein-coupled receptor recently identified as a marker of intestinal stem cells, marks a population of hair follicle stem cells that is actively proliferating and able to give rise to all cell types in the mouse hair follicle.

Uterine gland development is essential for successful embryo implantation, decidua formation and placental development. Here the authors demonstrate that neonatal Wnt-dependent Lgr5 expressing stem/progenitor cells at the tips of developing glands are indispensable for uterine gland development.

AQP5 is identified as a marker for pyloric stem cells in humans and mice, and stem cells in the AQP5⁺ compartment are shown to be a source of invasive gastric cancer in mouse models.

Better understanding of the genetic basis of acne can pave the way to more effective treatments. Here, the authors perform a genome-wide association study meta-analysis of >20,000 cases and identify 29 new acne susceptibility loci, uncovering genetic links to Mendelian hair and skin disorders and other complex traits.

Acne vulgaris is a chronic inflammation of the skin, the genetic basis of which is incompletely understood. Here, Petridis et al. perform GWAS and meta-analysis for acne in 26,722 individuals and identify 12 novel risk loci that implicate structure and maintenance of the skin in severe acne risk.

Multipotent stem cells expressing Lgr5 are known to generate all cell types of the intestinal epithelium (enterocytes, goblet cells, Paneth cells and enteroendocrine cells). A new study shows that Paneth cells have an essential role for intestinal crypt and stem cell maintenance by supplying essential niche signals to the Lgr5-expressing cells.

Lrg5⁺ is a protein which has been shown to mark cycling stem cells that renew the tissue of the intestine. Here, Lrg5⁺ stem cells were used in the establishment of long-term culture conditions capable of generating organoids with all the cell types and architecture of intestinal crypts present in adult mammals.

K. Lenhard Rudolph and colleagues report that conditional p53 deletion in the intestinal epithelium of aging mice impaired the depletion of chromosomal-instable stem cells and shortened the lifespan of telomere-dysfunctional mice without inducing tumor formation.

A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.

Psoriasis is an immune-mediated skin disease with a complex genetic architecture. Here, Elder and colleagues identify 16 novel psoriasis susceptibility loci using GWAS meta-analysis with a combined effective sample size of over 39,000 individuals.

A large-scale single-cell transcriptomic atlas of the non-human primate Macaca fascicularis encompasses over 1 million cells from 45 adult tissues.

Basal cell carcinoma has been shown to originate from activation of hedgehog signalling in interfollicular epidermal progenitor cells. Analyses of the early steps of basal cell carcinoma formation show that this process requires reprogramming of interfolliclular epidermal cells to an embryonic hair follicle progenitor-like fate, with concomitant Wnt pathway activation.

The Wnt signalling pathway has a central role in tissue development and tissue maintenance, but is frequently dysregulated in several types of cancer, particularly those of the digestive tract. Here, Barker and Clevers examine the recent progress in the development of Wnt inhibitors as anticancer drugs.

At each ovulation cycle, the single-layer epithelia that encapsulate mammalian ovaries undergo rupture and rapid repair. Recent studies have identified stem cell pools that ensure ovarian epithelial homeostasis, thus providing insights into the regulation of stem cell function and the contribution of stem cells to ovarian tumorigenesis.

Renewal and repair of the intestinal epithelium depend on small populations of intestinal stem cells. Specific markers for these stem cells have recently been discovered. This advance, together with the development of new technologies to track endogenous stem cell activity and to generate new epitheliaex vivo, is shedding light on the mechanisms underlying intestinal stem cell-driven homeostasis and regeneration.

Leushacke et al. provide insights into the role of Lgr5 cells in the oxyntic stomach, demonstrating that they label a subpopulation of chief cells that function as reserve stem cells during regeneration and cells-of-origin of gastric cancer.

Frontal fibrosing alopecia (FFA) features lichenoid cutaneous inflammation and scarring hair loss. Here, Tziotzios et al. identify four genetic loci associated with FFA by GWAS followed by Bayesian fine-mapping, co-localisation and HLA imputation which highlights HLA-B*07:02 as a risk factor.

Cutaneous squamous cell carcinomas is a growing problem but the driver genes causing this remain poorly defined. Here, the authors demonstrate that inactivating driver mutations in TGFBR1 and TGFBR2occur in vemurafenib-induced and sporadic cutaneous squamous cell carcinomas.

The mechanisms regulating the progression of benign tumors to malignant carcinomas remain incompletely understood. A new study identifies the transcription factor NR2F2 as a specific regulator of this transition that plays critical roles in the maintenance of the malignant tumor state.