Nature Cell Biology

Atamian, Alexander; Birtele, Marcella; Quadrato, Giorgia

doi: 10.1038/s41556-022-00890-3pmid: 35697780

Multiple methods for deriving human cortical organoids have been established in the past decade. A study now systematically compares patterning strategies and shows that combined WNT and dual SMAD inhibition is superior to dual SMAD inhibition alone in inducing robust cortical identity in 3D human pluripotent stem-cell aggregates.

Aranda, Sergi; Condemi, Livia; Di Croce, Luciano

doi: 10.1038/s41556-022-00937-5pmid: 35697784

Human naive pluripotent stem cells are generally believed to possess an unrestricted capacity to differentiate into both embryonic and extraembryonic lineages. However, two new studies now uncover a role for the Polycomb repressive complex 2 (PRC2) as a lineage gatekeeper that shields the potency of these cells.

Miklas, Jason Wayne; Brunet, Anne

doi: 10.1038/s41556-022-00908-wpmid: 35681007

The lysosome is an essential organelle that degrades extra- and intra-cellular components and acts as a signaling hub. A study in Caenorhabditis elegans now shows that the lysosome mediates inter-tissue communication from periphery to neurons to regulate lifespan via fatty acid breakdown and secretion.

Petrovic, Stefan; Hoelz, André

doi: 10.1038/s41556-022-00939-3pmid: 35681010

The nuclear pore complex (NPC) regulates transport of macromolecules into and out of the nucleus. A study now shows that mechanical force applied on the nucleus affects the transport rates across the NPC diffusion barrier, modulating the nuclear localization of certain cargos.

Faget, Douglas V.; Stewart, Sheila A.

doi: 10.1038/s41556-022-00930-ypmid: 35654838

Fibroblasts become activated during wound repair and rapidly return to a ‘resting’ state, and are thus critical for normal tissue homeostasis and tumour development. A new study now reveals an important pro-tumorigenic role for the stress response in cancer-associated fibroblasts that may offer a new opportunity to limit tumour progression.

Le, Phuong; Ahmed, Noorsher; Yeo, Gene W.

doi: 10.1038/s41556-022-00933-9pmid: 35697782

RNA processing plays a central role in accurately transmitting genetic information into functional RNA and protein regulators. To fully appreciate the RNA life-cycle, tools to observe RNA with high spatial and temporal resolution are critical. Here we review recent advances in RNA imaging and highlight how they will propel the field of RNA biology. We discuss current trends in RNA imaging and their potential to elucidate unanswered questions in RNA biology.

Huang, Yuwei; Zhang, Xing; Wang, Hong-Wei; Yu, Li

doi: 10.1038/s41556-022-00920-0pmid: 35654840

Various mechanisms contribute to membrane repair1, 2, 3, 4, 5, 6, 7–8 but the machinery that mediates the repair of large wounds on the plasma membrane is less clear. We found that shortly after membrane damage, Tetraspanin-enriched macrodomains are assembled around the damage site. Tetraspanin-enriched macrodomains are in the liquid-ordered phase and form a rigid ring around the damaged site. This restricts the spread of the damage and prevents membrane disintegration, thus facilitating membrane repair by other mechanisms. Functionally, Tetraspanin 4 helps cells mitigate damage caused by laser, detergent, pyroptosis and natural killer cells. We propose that assembly of Tetraspanin-enriched macrodomains creates a physical barrier to contain membrane damage.

Rothová, Michaela Mrugala; Nielsen, Alexander Valentin; Proks, Martin; Wong, Yan Fung; Riveiro, Alba Redo; Linneberg-Agerholm, Madeleine; David, Eyal; Amit, Ido; Trusina, Ala; Brickman, Joshua Mark

doi: 10.1038/s41556-022-00923-x

Kumar, Banushree; Navarro, Carmen; Winblad, Nerges; Schell, John P.; Zhao, Cheng; Weltner, Jere; Baqué-Vidal, Laura; Salazar Mantero, Angelo; Petropoulos, Sophie; Lanner, Fredrik; Elsässer, Simon J.

doi: 10.1038/s41556-022-00916-wpmid: 35637409

The first lineage choice in human embryo development separates trophectoderm from the inner cell mass. Naïve human embryonic stem cells are derived from the inner cell mass and offer possibilities to explore how lineage integrity is maintained. Here, we discover that polycomb repressive complex 2 (PRC2) maintains naïve pluripotency and restricts differentiation to trophectoderm and mesoderm lineages. Through quantitative epigenome profiling, we found that a broad gain of histone H3 lysine 27 trimethylation (H3K27me3) is a distinct feature of naïve pluripotency. We define shared and naïve-specific bivalent promoters featuring PRC2-mediated H3K27me3 concomitant with H3K4me3. Naïve bivalency maintains key trophectoderm and mesoderm transcription factors in a transcriptionally poised state. Inhibition of PRC2 forces naïve human embryonic stem cells into an ‘activated’ state, characterized by co-expression of pluripotency and lineage-specific transcription factors, followed by differentiation into either trophectoderm or mesoderm lineages. In summary, PRC2-mediated repression provides a highly adaptive mechanism to restrict lineage potential during early human development.

Zijlmans, Dick W.; Talon, Irene; Verhelst, Sigrid; Bendall, Adam; Van Nerum, Karlien; Javali, Alok; Malcolm, Andrew A.; van Knippenberg, Sam S. F. A.; Biggins, Laura; To, San Kit; Janiszewski, Adrian; Admiraal, Danielle; Knops, Ruth; Corthout, Nikky; Balaton, Bradley P.; Georgolopoulos, Grigorios; Panda, Amitesh; Bhanu, Natarajan V.; Collier, Amanda J.;