Complex Oscillatory Waves Emerging from Cortical Organoids Model Early Human Brain Network Development.

Abstract:

:Structural and transcriptional changes during early brain maturation follow fixed developmental programs defined by genetics. However, whether this is true for functional network activity remains unknown, primarily due to experimental inaccessibility of the initial stages of the living human brain. Here, we developed human cortical organoids that dynamically change cellular populations during maturation and exhibited consistent increases in electrical activity over the span of several months. The spontaneous network formation displayed periodic and regular oscillatory events that were dependent on glutamatergic and GABAergic signaling. The oscillatory activity transitioned to more spatiotemporally irregular patterns, and synchronous network events resembled features similar to those observed in preterm human electroencephalography. These results show that the development of structured network activity in a human neocortex model may follow stable genetic programming. Our approach provides opportunities for investigating and manipulating the role of network activity in the developing human cortex.

journal_name

Cell Stem Cell

journal_title

Cell stem cell

authors

Trujillo CA,Gao R,Negraes PD,Gu J,Buchanan J,Preissl S,Wang A,Wu W,Haddad GG,Chaim IA,Domissy A,Vandenberghe M,Devor A,Yeo GW,Voytek B,Muotri AR

doi

10.1016/j.stem.2019.08.002

subject

Has Abstract

pub_date

2019-10-03 00:00:00

pages

558-569.e7

issue

4

eissn

1934-5909

issn

1875-9777

pii

S1934-5909(19)30337-6

journal_volume

25

pub_type

杂志文章
  • Reprogramming can be a transforming experience.

    abstract::Since the inception of nuclear reprogramming, the parallels between this process and tumorigenesis have become increasingly apparent. Recent studies by Abad et al. and Ohnishi et al. have now formalized this connection by demonstrating that the same transcription factors used for reprogramming to pluripotency drive tu...

    journal_title:Cell stem cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.stem.2014.02.003

    authors: Hobbs RM,Polo JM

    更新日期:2014-03-06 00:00:00

  • Low incidence of DNA sequence variation in human induced pluripotent stem cells generated by nonintegrating plasmid expression.

    abstract::The utility of induced pluripotent stem cells (iPSCs) as models to study diseases and as sources for cell therapy depends on the integrity of their genomes. Despite recent publications of DNA sequence variations in the iPSCs, the true scope of such changes for the entire genome is not clear. Here we report the whole-g...

    journal_title:Cell stem cell

    pub_type: 杂志文章

    doi:10.1016/j.stem.2012.01.005

    authors: Cheng L,Hansen NF,Zhao L,Du Y,Zou C,Donovan FX,Chou BK,Zhou G,Li S,Dowey SN,Ye Z,NISC Comparative Sequencing Program.,Chandrasekharappa SC,Yang H,Mullikin JC,Liu PP

    更新日期:2012-03-02 00:00:00

  • From Skin to Brain: A Parkinson's Disease Patient Transplanted with His Own Cells.

    abstract::In a pioneering study in New England Journal of Medicine, Schweitzer et al. (2020) report on a patient with Parkinson's disease who received a graft of dopamine neurons obtained from in vitro differentiated induced pluripotent stem cells, derived from the patient's own skin fibroblasts, showing the feasibility of auto...

    journal_title:Cell stem cell

    pub_type: 杂志文章

    doi:10.1016/j.stem.2020.06.008

    authors: Parmar M,Björklund A

    更新日期:2020-07-02 00:00:00

  • Young and Restless: Expansion of Donor-Origin Mutant HSCs after Transplantation.

    abstract::In a study of young adults chosen as unrelated hematopoietic stem cell donors for patients with hematological malignancies, leukemia-associated mutations were detectable in cells from 44% of donors. Donor-origin mutant clones engrafted in recipients and expanded during the first 100 days after transplant, but donor-de...

    journal_title:Cell stem cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.stem.2020.01.022

    authors: Steensma DP

    更新日期:2020-03-05 00:00:00

  • The Isl1/Ldb1 Complex Orchestrates Genome-wide Chromatin Organization to Instruct Differentiation of Multipotent Cardiac Progenitors.

    abstract::Cardiac stem/progenitor cells hold great potential for regenerative therapies; however, the mechanisms regulating their expansion and differentiation remain insufficiently defined. Here we show that Ldb1 is a central regulator of genome organization in cardiac progenitor cells, which is crucial for cardiac lineage dif...

    journal_title:Cell stem cell

    pub_type: 杂志文章

    doi:10.1016/j.stem.2015.08.007

    authors: Caputo L,Witzel HR,Kolovos P,Cheedipudi S,Looso M,Mylona A,van IJcken WF,Laugwitz KL,Evans SM,Braun T,Soler E,Grosveld F,Dobreva G

    更新日期:2015-09-03 00:00:00

  • Primed for pluripotency.

    abstract::To date, pluripotent epiblast stem cells (EpiSCs) had only been derived from postimplantation mouse embryos. In this issue of Cell Stem Cell, Najm et al. (2011) demonstrate that EpiSCs can be routinely derived from preimplantation embryos, showing that both human and mouse blastocysts can produce the same class of pri...

    journal_title:Cell stem cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.stem.2011.02.009

    authors: Kunath T

    更新日期:2011-03-04 00:00:00

  • Single-Cell Transcriptomic Analyses of Cell Fate Transitions during Human Cardiac Reprogramming.

    abstract::Direct cellular reprogramming provides a powerful platform to study cell plasticity and dissect mechanisms underlying cell fate determination. Here, we report a single-cell transcriptomic study of human cardiac (hiCM) reprogramming that utilizes an analysis pipeline incorporating current data normalization methods, mu...

    journal_title:Cell stem cell

    pub_type: 杂志文章

    doi:10.1016/j.stem.2019.05.020

    authors: Zhou Y,Liu Z,Welch JD,Gao X,Wang L,Garbutt T,Keepers B,Ma H,Prins JF,Shen W,Liu J,Qian L

    更新日期:2019-07-03 00:00:00

  • Human adult testis-derived pluripotent stem cells: revealing plasticity from the germline.

    abstract::A recent publication in Nature by Conrad et al. (2008) reports the generation of pluripotent stem cells from isolated human adult testicular germ cells. This work identifies a new source of stem cells for potential autologous therapeutic applications in men. ...

    journal_title:Cell stem cell

    pub_type:

    doi:10.1016/j.stem.2008.10.009

    authors: Payne CJ,Braun RE

    更新日期:2008-11-06 00:00:00

  • Human embryonic stem cell-derived motor neurons are sensitive to the toxic effect of glial cells carrying an ALS-causing mutation.

    abstract::It has been proposed that human embryonic stem cells could be used to provide an inexhaustible supply of differentiated cell types for the study of disease processes. Although methods for differentiating embryonic stem cells into specific cell types have become increasingly sophisticated, the utility of the resulting ...

    journal_title:Cell stem cell

    pub_type: 杂志文章

    doi:10.1016/j.stem.2008.09.017

    authors: Di Giorgio FP,Boulting GL,Bobrowicz S,Eggan KC

    更新日期:2008-12-04 00:00:00

  • Tales from the Cryptkeeper: New Roles for Lats1/2 in Wnt-driven Homeostasis.

    abstract::In this issue of Cell Stem Cell, Li et al. (2020) reveal pivotal roles for Lats1/2 in adult, Wnt-mediated intestinal homeostasis through TEAD-dependent and -independent transcription. Loss of Lats1/2 mobilizes a previously unrecognized YAP/TAZ-Groucho/TLE interaction to suppress Wnt/TCF-mediated transcription, thereby...

    journal_title:Cell stem cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.stem.2020.04.011

    authors: Fu V,Guan KL

    更新日期:2020-05-07 00:00:00

  • Ground State Conditions Induce Rapid Reorganization of Core Pluripotency Factor Binding before Global Epigenetic Reprogramming.

    abstract::Mouse embryonic stem cells (mESCs) cultured under serum/LIF conditions exhibit heterogeneous expression of pluripotency-associated factors that can be overcome by two inhibitors (2i) of the MEK and GSK3 pathways. Several studies have shown that the "ground state" induced by 2i is characterized by global hypomethylatio...

    journal_title:Cell stem cell

    pub_type: 杂志文章

    doi:10.1016/j.stem.2015.07.005

    authors: Galonska C,Ziller MJ,Karnik R,Meissner A

    更新日期:2015-10-01 00:00:00

  • Generation of functional thymic epithelium from human embryonic stem cells that supports host T cell development.

    abstract::Inducing immune tolerance to prevent rejection is a key step toward successful engraftment of stem-cell-derived tissue in a clinical setting. Using human pluripotent stem cells to generate thymic epithelial cells (TECs) capable of supporting T cell development represents a promising approach to reach this goal; howeve...

    journal_title:Cell stem cell

    pub_type: 杂志文章

    doi:10.1016/j.stem.2013.04.004

    authors: Parent AV,Russ HA,Khan IS,LaFlam TN,Metzger TC,Anderson MS,Hebrok M

    更新日期:2013-08-01 00:00:00

  • Combined Single-Cell Functional and Gene Expression Analysis Resolves Heterogeneity within Stem Cell Populations.

    abstract::Heterogeneity within the self-renewal durability of adult hematopoietic stem cells (HSCs) challenges our understanding of the molecular framework underlying HSC function. Gene expression studies have been hampered by the presence of multiple HSC subtypes and contaminating non-HSCs in bulk HSC populations. To gain deep...

    journal_title:Cell stem cell

    pub_type: 杂志文章

    doi:10.1016/j.stem.2015.04.004

    authors: Wilson NK,Kent DG,Buettner F,Shehata M,Macaulay IC,Calero-Nieto FJ,Sánchez Castillo M,Oedekoven CA,Diamanti E,Schulte R,Ponting CP,Voet T,Caldas C,Stingl J,Green AR,Theis FJ,Göttgens B

    更新日期:2015-06-04 00:00:00

  • Profiling identifies precursor suspects: notch family again!

    abstract::Newborn neurons in the adult dentate gyrus pass through several distinct precursor and progenitor classes prior to differentiation. In this issue of Cell Stem Cell, Lugert et al. (2010) characterized their strikingly different proliferative behaviors after neurogenic stimuli or aging. ...

    journal_title:Cell stem cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.stem.2010.04.006

    authors: Breunig JJ,Rakic P

    更新日期:2010-05-07 00:00:00

  • Stem cells go soft: pliant substrate surfaces enhance motor neuron differentiation.

    abstract::Derivation of motor neurons from human pluripotent stem cells is inefficient and requires complex culture protocols. Recently in Nature Materials, Sun et al. (2014) report that differentiating human pluripotent stem cells on soft substrates increases the efficiency of mature motor neuron differentiation by altering cy...

    journal_title:Cell stem cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.stem.2014.05.007

    authors: Wang N

    更新日期:2014-06-05 00:00:00

  • Blood cells need glia, too: a new role for the nervous system in the bone marrow niche.

    abstract::Regulation of hematopoietic stem cell (HSC) dormancy by specific cell types in the hematopoietic niche remains poorly understood. Yamazaki et al. (2011) now report that nerve-associated nonmyelinating Schwann cells activate TGF-β to maintain dormant HSCs, suggesting that glia are novel players in the bone marrow niche...

    journal_title:Cell stem cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.stem.2011.11.016

    authors: Brückner K

    更新日期:2011-12-02 00:00:00

  • Mesenchymal stem cell homing: the devil is in the details.

    abstract::The study of MSC trafficking is clinically relevant for minimally invasive cell therapy to promote regeneration of damaged tissue, to treat inflammation, and to promote angiogenesis. However, these studies are complicated by the diverse methods used to culture, characterize, and deliver MSCs and by the variety of meth...

    journal_title:Cell stem cell

    pub_type: 杂志文章,评审

    doi:10.1016/j.stem.2009.02.001

    authors: Karp JM,Leng Teo GS

    更新日期:2009-03-06 00:00:00

  • Tet3 and DNA replication mediate demethylation of both the maternal and paternal genomes in mouse zygotes.

    abstract::With the exception of imprinted genes and certain repeats, DNA methylation is globally erased during preimplantation development. Recent studies have suggested that Tet3-mediated oxidation of 5-methylcytosine (5mC) and DNA replication-dependent dilution both contribute to global paternal DNA demethylation, but demethy...

    journal_title:Cell stem cell

    pub_type: 杂志文章

    doi:10.1016/j.stem.2014.09.002

    authors: Shen L,Inoue A,He J,Liu Y,Lu F,Zhang Y

    更新日期:2014-10-02 00:00:00

  • High-Throughput Screening Enhances Kidney Organoid Differentiation from Human Pluripotent Stem Cells and Enables Automated Multidimensional Phenotyping.

    abstract::Organoids derived from human pluripotent stem cells are a potentially powerful tool for high-throughput screening (HTS), but the complexity of organoid cultures poses a significant challenge for miniaturization and automation. Here, we present a fully automated, HTS-compatible platform for enhanced differentiation and...

    journal_title:Cell stem cell

    pub_type: 杂志文章

    doi:10.1016/j.stem.2018.04.022

    authors: Czerniecki SM,Cruz NM,Harder JL,Menon R,Annis J,Otto EA,Gulieva RE,Islas LV,Kim YK,Tran LM,Martins TJ,Pippin JW,Fu H,Kretzler M,Shankland SJ,Himmelfarb J,Moon RT,Paragas N,Freedman BS

    更新日期:2018-06-01 00:00:00

  • Mosaic Mutant Analysis Identifies PDGFRα/PDGFRβ as Negative Regulators of Adipogenesis.

    abstract::Adipocyte progenitors (APs) express platelet-derived growth factor receptors (PDGFRs), PDGFRα and PDGFRβ. Elevated PDGFRα signaling inhibits adipogenesis and promotes fibrosis; however, the function of PDGFRs in APs remains unclear. We combined lineage tracing and functional analyses in a sequential dual-recombinase a...

    journal_title:Cell stem cell

    pub_type: 杂志文章

    doi:10.1016/j.stem.2020.03.004

    authors: Sun C,Sakashita H,Kim J,Tang Z,Upchurch GM,Yao L,Berry WL,Griffin TM,Olson LE

    更新日期:2020-05-07 00:00:00

  • Mesenchymal Niche-Specific Expression of Cxcl12 Controls Quiescence of Treatment-Resistant Leukemia Stem Cells.

    abstract::Chronic myeloid leukemia (CML) originates in a hematopoietic stem cell (HSC) transformed by the breakpoint cluster region (BCR)-abelson (ABL) oncogene and is effectively treated with tyrosine kinase inhibitors (TKIs). TKIs do not eliminate disease-propagating leukemic stem cells (LSCs), suggesting a deeper understandi...

    journal_title:Cell stem cell

    pub_type: 杂志文章

    doi:10.1016/j.stem.2019.02.018

    authors: Agarwal P,Isringhausen S,Li H,Paterson AJ,He J,Gomariz Á,Nagasawa T,Nombela-Arrieta C,Bhatia R

    更新日期:2019-05-02 00:00:00

  • Ascl2 acts as an R-spondin/Wnt-responsive switch to control stemness in intestinal crypts.

    abstract::The Wnt signaling pathway controls stem cell identity in the intestinal epithelium and in many other adult organs. The transcription factor Ascl2 (a Wnt target gene) is a master regulator of intestinal stem cell identity. It is unclear how the continuous Wnt gradient along the crypt axis is translated into discrete ex...

    journal_title:Cell stem cell

    pub_type: 杂志文章

    doi:10.1016/j.stem.2014.12.006

    authors: Schuijers J,Junker JP,Mokry M,Hatzis P,Koo BK,Sasselli V,van der Flier LG,Cuppen E,van Oudenaarden A,Clevers H

    更新日期:2015-02-05 00:00:00

  • Decoupling of tumor-initiating activity from stable immunophenotype in HoxA9-Meis1-driven AML.

    abstract::Increasing evidence suggests tumors are maintained by cancer stem cells; however, their nature remains controversial. In a HoxA9-Meis1 (H9M) model of acute myeloid leukemia (AML), we found that tumor-initiating activity existed in three, immunophenotypically distinct compartments, corresponding to disparate lineages o...

    journal_title:Cell stem cell

    pub_type: 杂志文章

    doi:10.1016/j.stem.2012.01.004

    authors: Gibbs KD Jr,Jager A,Crespo O,Goltsev Y,Trejo A,Richard CE,Nolan GP

    更新日期:2012-02-03 00:00:00

  • The human egg is back.

    abstract::In a recent issue of Nature, Tachibana et al. (2009) conducted chromosomal transfer into recipient primate oocytes to yield live offspring or monkey ESCs with no contribution of donor mitochondria. The success of this technique may increase demand for human oocyte donation for research. ...

    journal_title:Cell stem cell

    pub_type: 杂志文章

    doi:10.1016/j.stem.2009.09.009

    authors: Cibelli J

    更新日期:2009-10-02 00:00:00

  • Collisions on the Busy DNA Highway Set Up Barriers for Reprogramming.

    abstract::Why most cells remain refractory to transcription factor (TF)-induced fate conversion remains largely mysterious, with the answers holding important instructions on how to effectively direct cell identities. In this issue of Cell Stem Cell, Babos et al. (2019) show that conflicts caused by simultaneous high transcript...

    journal_title:Cell stem cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.stem.2019.09.007

    authors: Hu X,Guo S

    更新日期:2019-10-03 00:00:00

  • Cellular reprogramming in pursuit of immortality.

    abstract::The discovery that phenotypic diversity among differentiated cells results from epigenetic and not genetic differences, and can be reset to restore pluripotency, promises revolutionary advances in medicine. I discuss how this and related seminal discoveries have brought us to an exciting future. ...

    journal_title:Cell stem cell

    pub_type: 杂志文章

    doi:10.1016/j.stem.2012.11.014

    authors: Surani MA

    更新日期:2012-12-07 00:00:00

  • Direct Induction of Trophoblast Stem Cells from Murine Fibroblasts.

    abstract::Trophoblast stem cells (TSCs) arise from the first cell fate decision in the developing embryo and generate extra-embryonic lineages, giving rise to the fetal portion of the placenta. Mouse embryonic and extra-embryonic lineages are strictly separated by a distinct epigenetic barrier, which is not fully overcome follo...

    journal_title:Cell stem cell

    pub_type: 杂志文章

    doi:10.1016/j.stem.2015.08.005

    authors: Kubaczka C,Senner CE,Cierlitza M,Araúzo-Bravo MJ,Kuckenberg P,Peitz M,Hemberger M,Schorle H

    更新日期:2015-11-05 00:00:00

  • Translational control: a new dimension in embryonic stem cell network analysis.

    abstract::Systems biology studies have revealed transcriptional networks and proteomic signatures critical for embryonic stem cell (ESC) function. In this issue of Cell Stem Cell, Sampath et al. (2008) demonstrate that translation is also differentially controlled in undifferentiated versus differentiated ESCs. ...

    journal_title:Cell stem cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.stem.2008.04.009

    authors: Chang WY,Stanford WL

    更新日期:2008-05-08 00:00:00

  • Clonal analysis via barcoding reveals diverse growth and differentiation of transplanted mouse and human mammary stem cells.

    abstract::Cellular barcoding offers a powerful approach to characterize the growth and differentiation activity of large numbers of cotransplanted stem cells. Here, we describe a lentiviral genomic-barcoding and analysis strategy and its use to compare the clonal outputs of transplants of purified mouse and human basal mammary ...

    journal_title:Cell stem cell

    pub_type: 杂志文章

    doi:10.1016/j.stem.2013.12.011

    authors: Nguyen LV,Makarem M,Carles A,Moksa M,Kannan N,Pandoh P,Eirew P,Osako T,Kardel M,Cheung AM,Kennedy W,Tse K,Zeng T,Zhao Y,Humphries RK,Aparicio S,Eaves CJ,Hirst M

    更新日期:2014-02-06 00:00:00

  • mTOR mediates Wnt-induced epidermal stem cell exhaustion and aging.

    abstract::Epidermal integrity is a complex process established during embryogenesis and maintained throughout the organism lifespan by epithelial stem cells. Although Wnt regulates normal epithelial stem cell renewal, aberrant Wnt signaling can contribute to cancerous growth. Here, we explored the consequences of persistent exp...

    journal_title:Cell stem cell

    pub_type: 杂志文章

    doi:10.1016/j.stem.2009.06.017

    authors: Castilho RM,Squarize CH,Chodosh LA,Williams BO,Gutkind JS

    更新日期:2009-09-04 00:00:00