... of differentiation and integrate knowledge from cell atlases. We present single-cell Type Order Parameters (scTOP): a statistical-physics-inspired approach for quantifying cell identity given a reference basis of cell types. scTOP can accurately classify cells, visualize developmental trajectories, and assess...

... and transcriptomic approaches to study self-organization of human ESCs (hESC) in two-dimensional (2D) culture. Morphogen dynamics were controlled via optogenetic activation of canonical Wnt/β-catenin signaling (optoWnt), which drove broad transcriptional changes and mesendoderm differentiation at high efficiency...

... requires a careful balance between cellular proliferation and differentiation. Premature or delayed differentiation, for instance, can result in tissue imbalance, malformation or malfunction. Despite seemingly rigid constraints on development, however, there is flexibility in both the timing...

... and medulloblastomas. It is suspected that these disorders arise in progenitor states of the CGN lineage, for which human models are lacking. Here, we have differentiated human hindbrain neuroepithelial stem (hbNES) cells to CGNs in vitro using soluble growth factors, recapitulating key progenitor states...

...Sophie E. Keegan; Julie Haskins; Andrew J. Simmonds; Sarah C. Hughes ABSTRACT Coordinated spatio-temporal regulation of the determination and differentiation of neural stem cells is essential for brain development. Failure to integrate multiple factors leads to defective brain structures or tumour...

... and transcriptional machinery of a cell to elicit qualitative transitions in its collective state. Single-cell RNA sequencing (scRNA-seq), which measures the distributions of possible transcriptional states in large populations of differentiating cells, provides an alternate view, in which development is marked...

... identity ( Chambers et al., 2020b ; Marra et al., 2019a , b ). Indeed, we found that esrrγa deficiency resulted in a decreased MCC cell number [marked by odf3b (also known as cimap1b ), an established marker of terminally differentiated MCCs], and co-injection of esrrγa RNA was sufficient to rescue...

.... The absence of Eomes and T at transcript and protein levels in the differentiated Eomes KO, T KO and dKO cells was confirmed using RT-PCR and western blotting, respectively. WT mESCs were from a F1G4 background ( George et al., 2007 ). Conditional Smad4 KO cells (Smad4CA) were provided by Prof...

.... Yan binds to common binding sites with higher affinity than Pnt ( Xu et al., 2000 ). Moreover, recent experiments suggest Yan and Pnt differentially interpret the structural syntax of enhancers and promoters ( Boisclair Lachance et al., 2018 ). This complexity is a consequence of cooperative...

.... The stoichiometry of this modification is tightly controlled throughout all stages of development, with both hypo/hyper O-GlcNAcylation resulting in broad defects. In this Primer, we discuss the role of O-GlcNAcylation in developmental processes from stem cell maintenance and differentiation to cell and tissue...

...Chunyang Ni; Michael Buszczak ABSTRACT Although differential transcription drives the development of multicellular organisms, the ultimate readout of a protein-coding gene is ribosome-dependent mRNA translation. Ribosomes were once thought of as uniform molecular machines, but emerging evidence...

...Christina Geraldine Kantzer; Wei Yang; David Grommisch; Kim Vikhe Patil; Kylie Hin-Man Mak; Vera Shirokova; Maria Genander ABSTRACT The regulatory circuits that coordinate epidermal differentiation during development are still not fully understood. Here, we report that the transcriptional regulator...

... a premature neuronal differentiation gene expression signature in ret wmr1/+ ENCCs. These results suggest that Ret signaling may regulate maintenance of a stem state in ENCCs. National Science Foundation http://dx.doi.org/10.13039/100000001 1942019 National Institutes of Health http...

... nephron progenitor exhaustion through their accelerated differentiation in pyrroline-5-carboxylate reductases 1 ( Pycr1 ) and 2 ( Pycr2 ) double-knockout kidneys. Pycr1 / Pycr2 -deficient progenitors showed normal cell survival, indicating no changes in cellular stress. Our results suggest that MAPK/ERK...

... differentiation. The heterozygous mutants were born with no pancreatic phenotype but displayed gradual acinar atrophy due to cell polarity defects in exocrine cells. Together, our findings imply a role for FAK in controlling the timing of pancreatic lineage commitment and/or differentiation in the embryonic...

... in these precursors exhibit a delayed onset and reduced level of SMC differentiation and peristaltic activity, as well as dilatation of the ureter and renal pelvis (hydroureternephrosis) at birth and at postnatal stages. Molecular profiling revealed a delayed and reduced expression of the myogenic driver gene Myocd...

... found that one factor in the middle of the cascade, END-1, which straddles the distinct events of specification and differentiation, functions in both processes. Finally, we reveal roles for key GATA factors in establishing spatial regulatory state domains by repressing other fates, thereby defining...

... of proliferation versus differentiation in the central nervous system . Cell Tissue Res. 359 , 187 - 200 . 10.1007/s00441-014-1895-8 Jang , J. , Han , D. , Golkaram , M. , Audouard , M. , Liu , G. , Bridges , D. , Hellander , S. , Chialastri , A. , Dey , S. S...

...Matthew J. Shannon; Jennet Baltayeva; Barbara Castellana; Jasmin Wächter; Gina L. McNeill; Ji Soo Yoon; Jenna Treissman; Hoa T. Le; Pascal M. Lavoie; Alexander G. Beristain ABSTRACT In early placental development, progenitor cytotrophoblasts (CTB) differentiate along one of two cellular...

...Alicia McCarthy; Kahini Sarkar; Elliot T. Martin; Maitreyi Upadhyay; Seoyeon Jang; Nathan D. Williams; Paolo E. Forni; Michael Buszczak; Prashanth Rangan ABSTRACT Gamete formation from germline stem cells (GSCs) is essential for sexual reproduction. However, the regulation of GSC differentiation...