Biology subjects

Carlein, C.

Publications and source records attributed to Carlein, C..

3 recordsLinked to original sources

bioRxiv2026

High-purity stem cell-derived β-cells recapitulate key transcriptional and functional features of human islets

Human pluripotent stem cell-derived islets (SC-islets) offer an excellent medium for human pancreatic disease modelling and mechanistic studies into diabetes. While substantial progress has been made in differentiation protocols, their implementation in different laboratories result in variable {beta}-cell proportions with contaminant non-endocrine and proliferative cell types. To date, no facility-level implementation exists for producing SC-islets that can be shipped and benchmarked across multiple sites. Here, we describe the scalable optimisation, standardization, and facility-level implementation of an established human stem cell differentiation strategy that consistently results in a high proportion of {beta}-cells, with up to 75% of cells co-expressing C-peptide and the pancreatic endocrine marker, ISL1. Functionally, SC-islets exhibit glucose-responsive calcium influx and insulin secretion, recapitulating key physiological {beta}-cell functions. Single-cell transcriptomic profiling reveals a simplified endocrine landscape dominated by {beta}-cells, with a striking transcriptional similarity to human primary {beta}-cells (Pearsons r2[~]0.9). We observe smaller fractions of - and enterochromaffin-like cells with very low levels of poly-hormonal or proliferating cell types (<3%). Taken together, we provide a well-defined, reproducible and accessible in vitro SC-islet platform benchmarked for functionality at multiple recipient sites.

cell biology↗

bioRxiv2024

Pancreatic islets undergo functional and morphological adaptation during development of Barth Syndrome

Barth syndrome is a multisystem genetic disorder caused by mutation in TAFAZZIN, a gene that encodes a phospholipid:lysophospholipid transacylase important for cardiolipin remodeling. Barth Syndrome patients suffer from a number of symptoms including early heart failure, fatigue, and systemic metabolic alterations, including hypoglycemia. The endocrine pancreas is central to glucose homeostasis, however, the impact of defective cardiolipin remodeling on pancreatic islet function and the consequences for systemic metabolism is unclear. Surprisingly, in a mouse model with global TAFAZZIN knockdown, we observed improved glucose tolerance compared to wildtype littermates. We show that pancreatic islet metabolism and secretory function are robustly maintained through various compensatory mechanisms including increased glucose uptake and increased mitochondrial volume. Transcriptomics analyses revealed increased expression of genes encoding proteins involved in N-acetylglucosamine synthesis and protein O-linked N-acetylglucosaminylation. These pathways might provide a molecular mechanism for coupling metabolic changes to mitochondrial volume regulation.

physiology↗

bioRxiv2024

Multicore-fiber microendoscopy for functional cellular in-organ imaging

Microendoscopy enables minimally invasive investigations of organs even within small cavities. Conventional microendoscopy is limited by probe size and often restricted to a single excitation wavelength. We developed and characterized a multichannel microendoscope as thin as 360 {micro}m and recorded functional cellular signals in-situ using custom written software for image processing. The endoscope had an effective resolution of 4.64 {micro}m and resolved subcellular structures of neurons. The system enabled analysis of in-situ calcium responses in murine tracheal brush cells and kidney podocytes. Additionally, ratiometric redox responses were recorded in whole, explanted organs and pancreatic islet culture. The flexibility and simplicity of our approach for imaging a variety of tissues and organs paves the way for in-vivo, longitudinal studies with cellular resolution.

bioengineering↗