An integrated transcriptomic cell atlas of human neural organoids.

Human neural organoids, generated from pluripotent stem cells in vitro, are useful tools to study human brain development, evolution and disease. However, it is unclear which parts of the human brain are covered by existing protocols, and it has been difficult to quantitatively assess organoid variation and fidelity. Here we integrate 36 single-cell transcriptomic datasets spanning 26 protocols into one integrated human neural organoid cell atlas totalling more than 1.

Programming human cell fate: overcoming challenges and unlocking potential through technological breakthroughs.

In recent years, there have been notable advancements in the ability to programme human cell identity, enabling us to design and manipulate cell function in a Petri dish. However, current protocols for generating target cell types often lack efficiency and precision, resulting in engineered cells that do not fully replicate the desired identity or functional output. This applies to different methods of cell programming, which face similar challenges that hinder progress and delay the achievement of a more favourable outcome.

Lineage recording in human cerebral organoids.

Induced pluripotent stem cell (iPSC)-derived organoids provide models to study human organ development. Single-cell transcriptomics enable highly resolved descriptions of cell states within these systems; however, approaches are needed to directly measure lineage relationships. Here we establish iTracer, a lineage recorder that combines reporter barcodes with inducible CRISPR-Cas9 scarring and is compatible with single-cell and spatial transcriptomics.

NGN2 induces diverse neuron types from human pluripotency.

Human neurons engineered from induced pluripotent stem cells (iPSCs) through neurogenin 2 (NGN2) overexpression are widely used to study neuronal differentiation mechanisms and to model neurological diseases. However, the differentiation paths and heterogeneity of emerged neurons have not been fully explored. Here, we used single-cell transcriptomics to dissect the cell states that emerge during NGN2 overexpression across a time course from pluripotency to neuron functional maturation.

The C-degron pathway eliminates mislocalized proteins and products of deubiquitinating enzymes.

Protein termini are determinants of protein stability. Proteins bearing degradation signals, or degrons, at their amino- or carboxyl-termini are eliminated by the N- or C-degron pathways, respectively. We aimed to elucidate the function of C-degron pathways and to unveil how normal proteomes are exempt from C-degron pathway-mediated destruction.

Combination of inductive effect of lipopolysaccharide and in situ mechanical conditioning for forming an autologous vascular graft in vivo.

Autologous vascular grafts have the advantages of better biocompatibility and prognosis. However, previous studies that implanted bare polymer tubes in animals to grow autologous tubular tissues were limited by their poor yield rates and stability. To enhance the yield rate of the tubular tissue, we employed a design with the addition of overlaid autologous whole blood scaffold containing lipopolysaccharides (LPS).

Recognition of the Diglycine C-End Degron by CRL2 Ubiquitin Ligase.

Aberrant proteins can be deleterious to cells and are cleared by the ubiquitin-proteasome system. A group of C-end degrons that are recognized by specific cullin-RING ubiquitin E3 ligases (CRLs) has recently been identified in some of these abnormal polypeptides. Here, we report three crystal structures of a CRL2 substrate receptor, KLHDC2, in complex with the diglycine-ending C-end degrons of two early-terminated selenoproteins and the N-terminal proteolytic fragment of USP1.

C-Terminal End-Directed Protein Elimination by CRL2 Ubiquitin Ligases.

The proteolysis-assisted protein quality control system guards the proteome from potentially detrimental aberrant proteins. How miscellaneous defective proteins are specifically eliminated and which molecular characteristics direct them for removal are fundamental questions. We reveal a mechanism, DesCEND (destruction via C-end degrons), by which CRL2 ubiquitin ligase uses interchangeable substrate receptors to recognize the unusual C termini of abnormal proteins (i.

A quantitative model for the rate-limiting process of UGA alternative assignments to stop and selenocysteine codons.

Ambiguity in genetic codes exists in cases where certain stop codons are alternatively used to encode non-canonical amino acids. In selenoprotein transcripts, the UGA codon may either represent a translation termination signal or a selenocysteine (Sec) codon. Translating UGA to Sec requires selenium and specialized Sec incorporation machinery such as the interaction between the SECIS element and SBP2 protein, but how these factors quantitatively affect alternative assignments of UGA has not been fully investigated.

SELENOPROTEINS. CRL2 aids elimination of truncated selenoproteins produced by failed UGA/Sec decoding.

Selenocysteine (Sec) is translated from the codon UGA, typically a termination signal. Codon duality extends the genetic code; however, the coexistence of two competing UGA-decoding mechanisms immediately compromises proteome fidelity. Selenium availability tunes the reassignment of UGA to Sec.

New abietane and seco-abietane diterpenes from the roots of Taiwania cryptomerioides.

Four new diterpenes, 3-oxosaprorthoquinone (1), 3-oxomicrostegiol (2), 3-oxoisotaxodione (3), and taiwaninal (4), together with two known compounds, 3-oxosapriparaquinone (5) and 6-dehydrohinokiol (6), were isolated from the roots of Taiwania cryptomerioides. The structures of 1-4 were principle elucidated based on spectral evidence.

New abietane-type diterpenes from the heartwood of Picea morrisonicola.

New abietane-type diterpenes, 15-acetoxy-7-oxodehydroabietic acid (1), picealactones A (2), B (3), and C (4), together with the known 7-oxodehydroabietic acid (5) were isolated and identified from the heartwood of Picea morrisonicola. The structures of 1-4 were determined on the basis of spectral data explanation. Compounds 2-4 possessed a rare 5-dehydro-18, 6-olide functionality.

Novel diterpenes from the heartwood of Chamaecyparis obtusa var. formosana.

Two novel diterpenes, obtusanal B (1) and obtusadione (2), along with obtusanal A (3), obtunone (4), 12-hydroxy-6,7-secoabieta-8,11,13-triene-6,7-dial, 8,12-dihydroxydielmentha-5,9-diene-7,11-dione and myrcene, isolated from the heartwood of Chamaecyparis obtusa var. formosana, were characterized by spectroscopic means, including 2D-NMR techniques. Compounds 1 and 2 are 7(6-->2)abeoabietane and 14(8-->9)abeoabietane type diterpenes, respectively.

Cadinane-type sesquiterpenes from the roots of Taiwania cryptomerioides Hayata.

Five new cadinane-type sesquiterpenes, 15-acetoxy-T-muurolol (1), isokhusinodiol (2), cadin-10(14)-ene-4beta,5alpha-diol (3), cadinane-4beta,5alpha,10beta-triol (4), and muurolane-4beta,5beta,10beta-triol (5), together with five known compounds, T-cadinol (6), T-muurolol (7), alpha-cadinol (8), delta-cadinol (9), and khusinodiol (10), were isolated from the roots of Taiwania cryptomerioides. The structure of the new constituents were elucidated through chemical and spectral studies.