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Kamil Slowikowski - One of the best experts on this subject based on the ideXlab platform.
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lymphocyte Innateness defined by transcriptional states reflects a balance between proliferation and effector functions
Nature Communications, 2019Co-Authors: Maria Gutierrezarcelus, Nikola Teslovich, Alex R Mola, Hyun Wha Kim, Susan K Hannes, Rafael B Polidoro, Aparna Nathan, Kamil SlowikowskiAbstract:How innate T cells (ITC), including invariant natural killer T (iNKT) cells, mucosal-associated invariant T (MAIT) cells, and γδ T cells, maintain a poised effector state has been unclear. Here we address this question using low-input and single-cell RNA-seq of human lymphocyte populations. Unbiased transcriptomic analyses uncover a continuous ‘Innateness gradient’, with adaptive T cells at one end, followed by MAIT, iNKT, γδ T and natural killer cells at the other end. Single-cell RNA-seq reveals four broad states of Innateness, and heterogeneity within canonical innate and adaptive populations. Transcriptional and functional data show that Innateness is characterized by pre-formed mRNA encoding effector functions, but impaired proliferation marked by decreased baseline expression of ribosomal genes. Together, our data shed new light on the poised state of ITC, in which Innateness is defined by a transcriptionally-orchestrated trade-off between rapid cell growth and rapid effector function. Innate T cells (ITC) contain many subsets and are poised to promptly respond to antigens and pathogens, but how this poised state is maintained is still unclear. Here the authors perform single-cell RNA-seq to align the various ITC subsets along an ‘Innateness gradient’ that is associated with changes in proliferation and effector functions.
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Lymphocyte Innateness defined by transcriptional states reflects a balance between proliferation and effector functions
Nature Publishing Group, 2019Co-Authors: Maria Gutierrez-arcelus, Nikola Teslovich, Alex R Mola, Kamil Slowikowski, Rafael B Polidoro, Aparna Nathan, Hyun Kim, Susan Hannes, Gerald F. M. Watts, Ilya KorsunskyAbstract:Innate T cells (ITC) contain many subsets and are poised to promptly respond to antigens and pathogens, but how this poised state is maintained is still unclear. Here the authors perform single-cell RNA-seq to align the various ITC subsets along an ‘Innateness gradient’ that is associated with changes in proliferation and effector functions
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a genome wide Innateness gradient defines the functional state of human innate t cells
bioRxiv, 2018Co-Authors: Maria Gutierrezarcelus, Nikola Teslovich, Alex R Mola, Hyun Wha Kim, Susan K Hannes, Kamil Slowikowski, Gfm Watts, Michael B Brenner, Soumya Raychaudhuri, Patrick J BrennanAbstract:Innate T cells (ITCs), including invariant natural killer T (iNKT) cells, mucosal-associated invariant T (MAIT) cells, and ; γδ T cell populations, use conserved antigen receptors generated by somatic recombination to respond to non-peptide antigens in an innate-like manner. Understanding where these cells fit in the scheme of immunity has been a puzzle since their discovery. Here, immunophenotyping of 101 individuals revealed that these populations account for as much as 25% of peripheral human T cells. To better understand these cells, we generated detailed gene expression profiles using low-input RNA-seq and confirmed key findings through protein-level and functional validation. Unbiased transcriptomic analyses revealed a continuous 9Innateness gradient9 with adaptive T cells at one end followed by MAIT, iNKT, Vδ1+ T, Vδ2+ T, and natural killer cells at the other end. Innateness was characterized by decreased expression of translational machinery genes and reduced proliferative potential, which allowed for prioritization of effector functions, including rapid cytokine and chemokine production, and cytotoxicity. Thus, global transcriptional programs uncovered rapid proliferation and rapid effector functions as competing goals that respectively define adaptive and innate states.
Nikola Teslovich - One of the best experts on this subject based on the ideXlab platform.
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lymphocyte Innateness defined by transcriptional states reflects a balance between proliferation and effector functions
Nature Communications, 2019Co-Authors: Maria Gutierrezarcelus, Nikola Teslovich, Alex R Mola, Hyun Wha Kim, Susan K Hannes, Rafael B Polidoro, Aparna Nathan, Kamil SlowikowskiAbstract:How innate T cells (ITC), including invariant natural killer T (iNKT) cells, mucosal-associated invariant T (MAIT) cells, and γδ T cells, maintain a poised effector state has been unclear. Here we address this question using low-input and single-cell RNA-seq of human lymphocyte populations. Unbiased transcriptomic analyses uncover a continuous ‘Innateness gradient’, with adaptive T cells at one end, followed by MAIT, iNKT, γδ T and natural killer cells at the other end. Single-cell RNA-seq reveals four broad states of Innateness, and heterogeneity within canonical innate and adaptive populations. Transcriptional and functional data show that Innateness is characterized by pre-formed mRNA encoding effector functions, but impaired proliferation marked by decreased baseline expression of ribosomal genes. Together, our data shed new light on the poised state of ITC, in which Innateness is defined by a transcriptionally-orchestrated trade-off between rapid cell growth and rapid effector function. Innate T cells (ITC) contain many subsets and are poised to promptly respond to antigens and pathogens, but how this poised state is maintained is still unclear. Here the authors perform single-cell RNA-seq to align the various ITC subsets along an ‘Innateness gradient’ that is associated with changes in proliferation and effector functions.
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Lymphocyte Innateness defined by transcriptional states reflects a balance between proliferation and effector functions
Nature Publishing Group, 2019Co-Authors: Maria Gutierrez-arcelus, Nikola Teslovich, Alex R Mola, Kamil Slowikowski, Rafael B Polidoro, Aparna Nathan, Hyun Kim, Susan Hannes, Gerald F. M. Watts, Ilya KorsunskyAbstract:Innate T cells (ITC) contain many subsets and are poised to promptly respond to antigens and pathogens, but how this poised state is maintained is still unclear. Here the authors perform single-cell RNA-seq to align the various ITC subsets along an ‘Innateness gradient’ that is associated with changes in proliferation and effector functions
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a genome wide Innateness gradient defines the functional state of human innate t cells
bioRxiv, 2018Co-Authors: Maria Gutierrezarcelus, Nikola Teslovich, Alex R Mola, Hyun Wha Kim, Susan K Hannes, Kamil Slowikowski, Gfm Watts, Michael B Brenner, Soumya Raychaudhuri, Patrick J BrennanAbstract:Innate T cells (ITCs), including invariant natural killer T (iNKT) cells, mucosal-associated invariant T (MAIT) cells, and ; γδ T cell populations, use conserved antigen receptors generated by somatic recombination to respond to non-peptide antigens in an innate-like manner. Understanding where these cells fit in the scheme of immunity has been a puzzle since their discovery. Here, immunophenotyping of 101 individuals revealed that these populations account for as much as 25% of peripheral human T cells. To better understand these cells, we generated detailed gene expression profiles using low-input RNA-seq and confirmed key findings through protein-level and functional validation. Unbiased transcriptomic analyses revealed a continuous 9Innateness gradient9 with adaptive T cells at one end followed by MAIT, iNKT, Vδ1+ T, Vδ2+ T, and natural killer cells at the other end. Innateness was characterized by decreased expression of translational machinery genes and reduced proliferative potential, which allowed for prioritization of effector functions, including rapid cytokine and chemokine production, and cytotoxicity. Thus, global transcriptional programs uncovered rapid proliferation and rapid effector functions as competing goals that respectively define adaptive and innate states.
Hyun Wha Kim - One of the best experts on this subject based on the ideXlab platform.
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lymphocyte Innateness defined by transcriptional states reflects a balance between proliferation and effector functions
Nature Communications, 2019Co-Authors: Maria Gutierrezarcelus, Nikola Teslovich, Alex R Mola, Hyun Wha Kim, Susan K Hannes, Rafael B Polidoro, Aparna Nathan, Kamil SlowikowskiAbstract:How innate T cells (ITC), including invariant natural killer T (iNKT) cells, mucosal-associated invariant T (MAIT) cells, and γδ T cells, maintain a poised effector state has been unclear. Here we address this question using low-input and single-cell RNA-seq of human lymphocyte populations. Unbiased transcriptomic analyses uncover a continuous ‘Innateness gradient’, with adaptive T cells at one end, followed by MAIT, iNKT, γδ T and natural killer cells at the other end. Single-cell RNA-seq reveals four broad states of Innateness, and heterogeneity within canonical innate and adaptive populations. Transcriptional and functional data show that Innateness is characterized by pre-formed mRNA encoding effector functions, but impaired proliferation marked by decreased baseline expression of ribosomal genes. Together, our data shed new light on the poised state of ITC, in which Innateness is defined by a transcriptionally-orchestrated trade-off between rapid cell growth and rapid effector function. Innate T cells (ITC) contain many subsets and are poised to promptly respond to antigens and pathogens, but how this poised state is maintained is still unclear. Here the authors perform single-cell RNA-seq to align the various ITC subsets along an ‘Innateness gradient’ that is associated with changes in proliferation and effector functions.
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a genome wide Innateness gradient defines the functional state of human innate t cells
bioRxiv, 2018Co-Authors: Maria Gutierrezarcelus, Nikola Teslovich, Alex R Mola, Hyun Wha Kim, Susan K Hannes, Kamil Slowikowski, Gfm Watts, Michael B Brenner, Soumya Raychaudhuri, Patrick J BrennanAbstract:Innate T cells (ITCs), including invariant natural killer T (iNKT) cells, mucosal-associated invariant T (MAIT) cells, and ; γδ T cell populations, use conserved antigen receptors generated by somatic recombination to respond to non-peptide antigens in an innate-like manner. Understanding where these cells fit in the scheme of immunity has been a puzzle since their discovery. Here, immunophenotyping of 101 individuals revealed that these populations account for as much as 25% of peripheral human T cells. To better understand these cells, we generated detailed gene expression profiles using low-input RNA-seq and confirmed key findings through protein-level and functional validation. Unbiased transcriptomic analyses revealed a continuous 9Innateness gradient9 with adaptive T cells at one end followed by MAIT, iNKT, Vδ1+ T, Vδ2+ T, and natural killer cells at the other end. Innateness was characterized by decreased expression of translational machinery genes and reduced proliferative potential, which allowed for prioritization of effector functions, including rapid cytokine and chemokine production, and cytotoxicity. Thus, global transcriptional programs uncovered rapid proliferation and rapid effector functions as competing goals that respectively define adaptive and innate states.
Elizabeth S Spelke - One of the best experts on this subject based on the ideXlab platform.
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Innateness learning and rationality
Child Development Perspectives, 2009Co-Authors: Elizabeth S Spelke, Katherine D KinzlerAbstract:— J. P. Spencer et al. (2009) ask readers to reject the nativist–empiricist dialogue and adopt a new theoretical perspective on cognition, focusing on “developmental process.” This commentary argues that the dialogue between nativism and empiricism is a rich source of insight into the nature and development of human knowledge. Indeed, the dialogue is entering a new and exciting phase, in which new methods of controlled rearing and of cognitive neuroscience, and new conceptual tools for understanding learning, allow exploration of how human concepts emerge through the interaction of innate cognitive structures shaped by natural selection, with statistical learning processes shaped by specific encounters with the world. This approach fosters new, interdisciplinary research that promises to increase dramatically understanding of human knowledge.
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Innateness learniffb and rationality
2009Co-Authors: Elizabeth S Spelke, Katherine D KinzlerAbstract:nssrRAcr-/. P. Spencer et aI. (2OO9) tl,sk readers to reject the rurtit:istremltiritist dialogue and adopt a new th.eoretica.l perspecthte on cognition, focwing on "d'eaelopmcntal process.'o This commcntaty argu'es that the d'fuIague beween natitsisrn and. empiricism is a rich souree of iruWht into the ndture and, d.eaelapm'ent of hwnanlm'owledge. Indced,, the d,ialogue is efiering a neur and' ercitittg ph.a.se, in which new mcthnds of controll'ed' rearhg a,nd of cognitfue neurosci.ence, and, new conceptual tools for wd,erstand,fury learnfury, alknn explaration of how hwrutn concepts en.erge through the interaction of i.nnate cogni' thse structures shaped. by natwal sel'ecrtono uirh statistical Learnirtg processes shaped. by specific encounters wilh the world.. This approach fosters new, interd.isciplinaty research that promises to increase drama'tically und,erstanding of human lm.owlcdge.
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Innateness learning and the development of object representation
Developmental Science, 1999Co-Authors: Elizabeth S SpelkeAbstract:This is a curious debate. On one side, Baillargeon argues that theories couched in the terms of the nativist± empiricist dialogue are wellsprings of empirical hypotheses and findings. She illustrates this point by describing a series of elegant experiments investigating infants' developing knowledge about the relationships between objects and their supports, containers or occluders. In a particularly exciting turn, she reports new objectlearning experiments in which she both observes and manipulates the growth of infants' knowledge of these relationships. On the other side, Smith argues that theories couched in the terms of the nativist±empiricist dialogue are dead ends. She illustrates this point by describing a series of elegant experiments investigating young children's developing knowledge about the relationships between objects and the words and expressions people use to describe them. In a particularly exciting turn, she reports new word-learning experiments in which she both observes and manipulates the growth of children's knowledge of these relationships. Why do such closely parallel research programs lead their authors to such apparently different conclusions? I see three sources to this debate. First, Baillargeon and Smith disagree over the terms of the nativist± empiricist dialogue, and particularly over the nature of nativist claims. Second, they disagree about the role science can play in illuminating human knowledge. Finally, they disagree about the questions that studies of cognitive development should ask and the questions that should be postponed. I consider each of these differences in turn. Baillargeon and Smith give different meanings to the term `innate'. For Baillargeon, as for generations of contributors to the nativist±empiricist dialogue, `innate' means not learned. For much of Smith's paper, in contrast, `innate' means preformed. The vast difference between these meanings can be seen through Smith's chosen example of fingers and toes: body parts are not preformed in the fertilized egg, but neither are they learned by the developing child as she observes other people's body parts or encounters situations that require them. In the tradition of the nativist±empiricist dialogue, body parts pass the two central tests for Innateness: their structure emerges in advance of their function, and their structure is not subsequently shaped by the organism's encounters with the external objects and situations to which it applies. When Smith claims that knowledge develops as do fingers and toes, therefore, the most radical nativist would not disagree. Although earlier contributors to the nativist± empiricist dialogue were careful to maintain the distinction between nativism and preformationism, a number of recent discussions have tended to conflate these claims (e.g. Thelen & Smith, 1993; Elman et al., 1996; Quartz & Sejnowski, 1997; see Spelke & Newport, 1998, for discussion). Because nativists are not preformationists, this conflation produces arguments directed against no real adversary, and it sidesteps the core questions at issue concerning the origins and development of knowledge: To what degree is our knowledge shaped by encounters with the things known? How variable is the knowledge of people who live in different circumstances? To what degree can we influence the conceptions of our children, by changing the environments in which they grow? The research described by Baillargeon and by Smith testifies to the continued fruitfulness of these questions, and to the vitality of the centuriesold dialogue within which the questions have been articulated and refined.
Mark S Seidenberg - One of the best experts on this subject based on the ideXlab platform.
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language learning and Innateness some implications of compounds research
Cognitive Psychology, 2003Co-Authors: Todd R Haskell, Maryellen C Macdonald, Mark S SeidenbergAbstract:In noun compounds in English, the modifying noun may be singular (mouse-eater) or an irregularly inflected plural (mice-eater), but regularly inflected plurals are dispreferred (*rats-eater). This phenomenon has been taken as strong evidence for dual-mechanism theories of lexical representations, which hold that regular (rule-governed) and irregular (exception) items are generated by qualitatively different and innately specified mechanisms. Using corpus analyses, behavioral studies, and computational modeling, we show that the rule-versus-exceptions approach makes a number of incorrect predictions. We propose a new account in which the acceptability of modifiers is determined by a constraint satisfaction process modulated by semantic, phonological, and other factors. The constraints are acquired by the child via general purpose learning algorithms, based on noun compounds and other constructions in the input. The account obviates the regular/irregular dichotomy while simultaneously providing a superior account of the data.