SIMS: A deep-learning label transfer tool for single-cell RNA sequencing analysis DOI Creative Commons
Jesus Gonzalez-Ferrer, Julian Lehrer, Ash O’Farrell

et al.

Cell Genomics, Journal Year: 2024, Volume and Issue: 4(6), P. 100581 - 100581

Published: May 31, 2024

Cell atlases serve as vital references for automating cell labeling in new samples, yet existing classification algorithms struggle with accuracy. Here we introduce SIMS (scalable, interpretable machine learning single cell), a low-code data-efficient pipeline single-cell RNA classification. We benchmark against datasets from different tissues and species. demonstrate SIMS's efficacy classifying cells the brain, achieving high accuracy even small training sets (<3,500 cells) across samples. accurately predicts neuronal subtypes developing shedding light on genetic changes during differentiation postmitotic fate refinement. Finally, apply to of cortical organoids predict identities uncover variations between lines. identifies cell-line differences misannotated lineages human derived pluripotent stem Altogether, show that is versatile robust tool cell-type datasets.

Language: Английский

Spatially resolved transcriptomics: a comprehensive review of their technological advances, applications, and challenges DOI Creative Commons

Mengnan Cheng,

Yujia Jiang, Jiangshan Xu

et al.

Journal of genetics and genomics/Journal of Genetics and Genomics, Journal Year: 2023, Volume and Issue: 50(9), P. 625 - 640

Published: March 27, 2023

The ability to explore life kingdoms is largely driven by innovations and breakthroughs in technology, from the invention of microscope 350 years ago recent emergence single-cell sequencing, which scientific community has been able visualize at an unprecedented resolution. Most recently, Spatially Resolved Transcriptomics (SRT) technologies have filled gap probing spatial or even three-dimensional organization molecular foundation behind mysteries life, including origin different cellular populations developed totipotent cells human diseases. In this review, we introduce progress challenges on SRT perspectives bioinformatic tools, as well representative applications. With currently fast-moving promising results early adopted research projects, can foresee bright future such new tools understanding most profound analytical level.

Language: Английский

Citations

75
Modeling blood-brain barrier formation and cerebral cavernous malformations in human PSC-derived organoids DOI
Lan T.M. Dao, Zhen You, Lu Lu

et al.

Cell stem cell, Journal Year: 2024, Volume and Issue: 31(6), P. 818 - 833.e11

Published: May 15, 2024

Language: Английский

Citations

39
Human fetal brain self-organizes into long-term expanding organoids DOI Creative Commons
Delilah Hendriks, Anna Pagliaro, Francesco Andreatta

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(3), P. 712 - 732.e38

Published: Jan. 8, 2024

Human brain development involves an orchestrated, massive neural progenitor expansion while a multi-cellular tissue architecture is established. Continuously expanding organoids can be grown directly from multiple somatic tissues, yet to date, solely established pluripotent stem cells. Here, we show that healthy human fetal in vitro self-organizes into (FeBOs), phenocopying aspects of vivo cellular heterogeneity and complex organization. FeBOs expanded over long time periods. FeBO growth requires maintenance integrity, which ensures production tissue-like extracellular matrix (ECM) niche, ultimately endowing expansion. lines derived different areas the central nervous system (CNS), including dorsal ventral forebrain, preserve their regional identity allow probe positional identity. Using CRISPR-Cas9, showcase generation syngeneic mutant for study cancer. Taken together, constitute complementary CNS organoid platform.

Language: Английский

Citations

36
Brain Chimeroids reveal individual susceptibility to neurotoxic triggers DOI
Noelia Antón-Bolaños, Irene Faravelli, Tyler Faits

et al.

Nature, Journal Year: 2024, Volume and Issue: 631(8019), P. 142 - 149

Published: June 26, 2024

Language: Английский

Citations

35
An integrated transcriptomic cell atlas of human neural organoids DOI Creative Commons
Zhisong He, Leander Dony, Jonas Simon Fleck

et al.

Nature, Journal Year: 2024, Volume and Issue: 635(8039), P. 690 - 698

Published: Nov. 20, 2024

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 covered by existing protocols, has been difficult quantitatively assess organoid variation fidelity. Here we integrate 36 single-cell transcriptomic datasets spanning 26 protocols into one integrated cell atlas totalling more than 1.7 million cells1–26. Mapping developing references27–30 shows primary types states that have estimates similarity between counterparts across protocols. We provide a programmatic interface browse query new datasets, showcase power annotate evaluate Finally, show can be used as diverse control cohort compare models disease, identifying genes pathways may underlie pathological mechanisms with models. The will fidelity, characterize perturbed diseased facilitate protocol development. A integrating counterparts, showing potential fidelity

Language: Английский

Citations

23
Generation of human cerebral organoids with a structured outer subventricular zone DOI Creative Commons
Ryan Walsh, Raffaele Luongo, Elisa Giacomelli

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(4), P. 114031 - 114031

Published: April 1, 2024

Outer radial glia (oRG) emerge as cortical progenitor cells that support the development of an enlarged outer subventricular zone (oSVZ) and expansion neocortex. The in vitro generation oRG is essential to investigate underlying mechanisms human neocortical expansion. By activating STAT3 signaling pathway using leukemia inhibitory factor (LIF), which not expressed guided organoids, we define a organoid differentiation method from pluripotent stem (hPSCs) recapitulates pool into oSVZ. oSVZ comprises expressing specific markers such GFAP, LIFR, HOPX, closely matching fetal oRG. Finally, incorporating neural crest-derived LIF-producing pericytes organoids effects LIF treatment. These data indicate increasing cellular complexity microenvironment promotes emergence supports platform study hPSC-derived brain routinely.

Language: Английский

Citations

17
Modelling viral encephalitis caused by herpes simplex virus 1 infection in cerebral organoids DOI Creative Commons
Agnieszka Rybak‐Wolf, Emanuel Wyler, Tancredi Massimo Pentimalli

et al.

Nature Microbiology, Journal Year: 2023, Volume and Issue: 8(7), P. 1252 - 1266

Published: June 22, 2023

Abstract Herpes simplex encephalitis is a life-threatening disease of the central nervous system caused by herpes viruses (HSVs). Following standard care with antiviral acyclovir treatment, most patients still experience various neurological sequelae. Here we characterize HSV-1 infection human brain organoids combining single-cell RNA sequencing, electrophysiology and immunostaining. We observed strong perturbations tissue integrity, neuronal function cellular transcriptomes. Under treatment viral replication was stopped, but did not prevent HSV-1-driven defects such as damage processes neuroepithelium. Unbiased analysis pathways deregulated upon revealed tumour necrosis factor activation potential causal factor. Combination anti-inflammatory drugs necrostatin-1 or bardoxolone methyl prevented damages infection, indicating that tuning inflammatory response in acute may improve current therapeutic strategies.

Language: Английский

Citations

40
Interpreting non-coding disease-associated human variants using single-cell epigenomics DOI
Kyle J. Gaulton, Sebastian Preißl, Bing Ren

et al.

Nature Reviews Genetics, Journal Year: 2023, Volume and Issue: 24(8), P. 516 - 534

Published: May 9, 2023

Language: Английский

Citations

39
Non-synaptic function of the autism spectrum disorder-associated gene SYNGAP1 in cortical neurogenesis DOI
Marcella Birtele,

Ashley Del Dosso,

Tiantian Xu

et al.

Nature Neuroscience, Journal Year: 2023, Volume and Issue: 26(12), P. 2090 - 2103

Published: Nov. 9, 2023

Language: Английский

Citations

38
LIF signaling regulates outer radial glial to interneuron fate during human cortical development DOI Creative Commons
Madeline G. Andrews, Clara Siebert, Li Wang

et al.

Cell stem cell, Journal Year: 2023, Volume and Issue: 30(10), P. 1382 - 1391.e5

Published: Sept. 5, 2023

Radial glial (RG) development is essential for cerebral cortex growth and organization. In humans, the outer radial glia (oRG) subtype expanded gives rise to diverse neurons glia. However, mechanisms regulating oRG differentiation are unclear. cells express leukemia-inhibitory factor (LIF) receptors during neurogenesis, consistent with a role in stem cell self-renewal, LIF perturbation impacts proliferation cortical tissue organoids. Surprisingly, treatment also increases production of inhibitory interneurons (INs) cultures. Comparative transcriptomic analysis identifies that enhanced IN population resembles INs produced caudal ganglionic eminence. To evaluate whether could arise from oRGs, we isolated primary cultured them LIF. We observed an increase abundance following treatment. Our observations suggest signaling regulates capacity generate INs.

Language: Английский

Citations

33