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Book ; Thesis: Stem cells, differentiation and nuclear reprogramming

Pawlak, Mathias

the roles of Klf4 and geminin

2008

Author's details	[presented by Mathias Pawlak]
Subject code	616.027
Language	English
Size	124 S., Ill., graph. Darst., 30 cm
Publishing country	Germany
Document type	Book ; Thesis
Thesis / German Habilitation thesis	Heidelberg, Univ., Diss., 2008
HBZ-ID	HT016219888
Database	Catalogue ZB MED Medicine, Health

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Article ; Online: Cytokines and transcription factors in the differentiation of CD4

Pawlak, Mathias / Ho, Allen W / Kuchroo, Vijay K

Current opinion in immunology

2020 Volume 67, Page(s) 57–67

Abstract: ... ...

Abstract	CD4
MeSH term(s)	Animals ; Autoimmunity/immunology ; CD4-Positive T-Lymphocytes/immunology ; Cell Differentiation/immunology ; Cytokines/immunology ; Humans ; Inflammation/immunology ; Transcription Factors/immunology
Chemical Substances	Cytokines ; Transcription Factors
Language	English
Publishing date	2020-10-08
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	1035767-1
ISSN	1879-0372 ; 0952-7915
ISSN (online)	1879-0372
ISSN	0952-7915
DOI	10.1016/j.coi.2020.09.001
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Zs.A 2773: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: A mouse DRG genetic toolkit reveals morphological and physiological diversity of somatosensory neuron subtypes.

Qi, Lijun / Iskols, Michael / Shi, David / Reddy, Pranav / Walker, Christopher / Lezgiyeva, Karina / Voisin, Tiphaine / Pawlak, Mathias / Kuchroo, Vijay K / Chiu, Isaac M / Ginty, David D / Sharma, Nikhil

Cell

2024 Volume 187, Issue 6, Page(s) 1508–1526.e16

Abstract: Dorsal root ganglia (DRG) somatosensory neurons detect mechanical, thermal, and chemical stimuli acting on the body. Achieving a holistic view of how different DRG neuron subtypes relay neural signals from the periphery to the CNS has been challenging ... ...

Abstract	Dorsal root ganglia (DRG) somatosensory neurons detect mechanical, thermal, and chemical stimuli acting on the body. Achieving a holistic view of how different DRG neuron subtypes relay neural signals from the periphery to the CNS has been challenging with existing tools. Here, we develop and curate a mouse genetic toolkit that allows for interrogating the properties and functions of distinct cutaneous targeting DRG neuron subtypes. These tools have enabled a broad morphological analysis, which revealed distinct cutaneous axon arborization areas and branching patterns of the transcriptionally distinct DRG neuron subtypes. Moreover, in vivo physiological analysis revealed that each subtype has a distinct threshold and range of responses to mechanical and/or thermal stimuli. These findings support a model in which morphologically and physiologically distinct cutaneous DRG sensory neuron subtypes tile mechanical and thermal stimulus space to collectively encode a wide range of natural stimuli.
MeSH term(s)	Animals ; Mice ; Ganglia, Spinal/cytology ; Sensory Receptor Cells/cytology ; Single-Cell Gene Expression Analysis ; Skin/innervation
Language	English
Publishing date	2024-03-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2024.02.006
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Article: A DRG genetic toolkit reveals molecular, morphological, and functional diversity of somatosensory neuron subtypes.

Qi, Lijun / Iskols, Michael / Shi, David / Reddy, Pranav / Walker, Christopher / Lezgiyeva, Karina / Voisin, Tiphaine / Pawlak, Mathias / Kuchroo, Vijay K / Chiu, Isaac / Ginty, David D / Sharma, Nikhil

bioRxiv : the preprint server for biology

2023

Abstract: Mechanical and thermal stimuli acting on the skin are detected by morphologically and physiologically distinct sensory neurons of the dorsal root ganglia (DRG). Achieving a holistic view of how this diverse neuronal population relays sensory information ... ...

Abstract	Mechanical and thermal stimuli acting on the skin are detected by morphologically and physiologically distinct sensory neurons of the dorsal root ganglia (DRG). Achieving a holistic view of how this diverse neuronal population relays sensory information from the skin to the central nervous system (CNS) has been challenging with existing tools. Here, we used transcriptomic datasets of the mouse DRG to guide development and curation of a genetic toolkit to interrogate transcriptionally defined DRG neuron subtypes. Morphological analysis revealed unique cutaneous axon arborization areas and branching patterns of each subtype. Physiological analysis showed that subtypes exhibit distinct thresholds and ranges of responses to mechanical and/or thermal stimuli. The somatosensory neuron toolbox thus enables comprehensive phenotyping of most principal sensory neuron subtypes. Moreover, our findings support a population coding scheme in which the activation thresholds of morphologically and physiologically distinct cutaneous DRG neuron subtypes tile multiple dimensions of stimulus space.
Language	English
Publishing date	2023-04-23
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.04.22.537932
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Article ; Online: De novo DNA methylation by Dnmt3a and Dnmt3b is dispensable for nuclear reprogramming of somatic cells to a pluripotent state.

Pawlak, Mathias / Jaenisch, Rudolf

Genes & development

2011 Volume 25, Issue 10, Page(s) 1035–1040

Abstract: Induced pluripotent stem cells (iPSCs) are generated from somatic cells by the transduction of defined transcription factors, and this process involves dynamic changes in DNA methylation. While the reprogramming of somatic cells is accompanied by ... ...

Abstract	Induced pluripotent stem cells (iPSCs) are generated from somatic cells by the transduction of defined transcription factors, and this process involves dynamic changes in DNA methylation. While the reprogramming of somatic cells is accompanied by demethylation of pluripotency genes, the functional importance of de novo DNA methylation has not been clarified. Here, using loss-of-function studies, we generated iPSCs from fibroblasts that were deficient in de novo DNA methylation mediated by Dnmt3a and Dnmt3b. These iPSCs reactivated pluripotency genes, underwent self-renewal, and showed restricted developmental potential that was rescued upon reintroduction of Dnmt3a and Dnmt3b. We conclude that de novo DNA methylation by Dnmt3a and Dnmt3b is dispensable for nuclear reprogramming of somatic cells.
MeSH term(s)	Animals ; Cells, Cultured ; Cellular Reprogramming/genetics ; Cellular Reprogramming/physiology ; DNA (Cytosine-5-)-Methyltransferases/deficiency ; DNA (Cytosine-5-)-Methyltransferases/genetics ; DNA (Cytosine-5-)-Methyltransferases/metabolism ; DNA Methylation ; DNA Methyltransferase 3A ; Fibroblasts/cytology ; Fibroblasts/enzymology ; Gene Deletion ; Mice ; Mice, SCID ; Pluripotent Stem Cells/cytology ; Pluripotent Stem Cells/physiology ; DNA Methyltransferase 3B
Chemical Substances	Dnmt3a protein, mouse ; DNA (Cytosine-5-)-Methyltransferases (EC 2.1.1.37) ; DNA Methyltransferase 3A (EC 2.1.1.37)
Language	English
Publishing date	2011-05-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	806684-x
ISSN	1549-5477 ; 0890-9369
ISSN (online)	1549-5477
ISSN	0890-9369
DOI	10.1101/gad.2039011
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Zs.A 2292: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Stem-like intestinal Th17 cells give rise to pathogenic effector T cells during autoimmunity.

Schnell, Alexandra / Huang, Linglin / Singer, Meromit / Singaraju, Anvita / Barilla, Rocky M / Regan, Brianna M L / Bollhagen, Alina / Thakore, Pratiksha I / Dionne, Danielle / Delorey, Toni M / Pawlak, Mathias / Meyer Zu Horste, Gerd / Rozenblatt-Rosen, Orit / Irizarry, Rafael A / Regev, Aviv / Kuchroo, Vijay K

Cell

2021 Volume 184, Issue 26, Page(s) 6281–6298.e23

Abstract: While intestinal Th17 cells are critical for maintaining tissue homeostasis, recent studies have implicated their roles in the development of extra-intestinal autoimmune diseases including multiple sclerosis. However, the mechanisms by which tissue Th17 ... ...

Abstract	While intestinal Th17 cells are critical for maintaining tissue homeostasis, recent studies have implicated their roles in the development of extra-intestinal autoimmune diseases including multiple sclerosis. However, the mechanisms by which tissue Th17 cells mediate these dichotomous functions remain unknown. Here, we characterized the heterogeneity, plasticity, and migratory phenotypes of tissue Th17 cells in vivo by combined fate mapping with profiling of the transcriptomes and TCR clonotypes of over 84,000 Th17 cells at homeostasis and during CNS autoimmune inflammation. Inter- and intra-organ single-cell analyses revealed a homeostatic, stem-like TCF1
MeSH term(s)	Animals ; Autoimmunity ; Cell Movement ; Clone Cells ; Encephalomyelitis, Autoimmune, Experimental/immunology ; Granulocyte-Macrophage Colony-Stimulating Factor/metabolism ; Homeostasis ; Humans ; Interferon-gamma/metabolism ; Interleukin-17/metabolism ; Intestines/immunology ; Mice, Inbred C57BL ; Organ Specificity ; RNA/metabolism ; RNA-Seq ; Receptors, Antigen, T-Cell/metabolism ; Receptors, CXCR6/metabolism ; Receptors, Interleukin/metabolism ; Reproducibility of Results ; Signaling Lymphocytic Activation Molecule Family/metabolism ; Single-Cell Analysis ; Spleen/metabolism ; Stem Cells/metabolism ; Th17 Cells/immunology ; Mice
Chemical Substances	CXCR6 protein, human ; IL23R protein, human ; Interleukin-17 ; Receptors, Antigen, T-Cell ; Receptors, CXCR6 ; Receptors, Interleukin ; SLAMF6 protein, human ; Signaling Lymphocytic Activation Molecule Family ; RNA (63231-63-0) ; Interferon-gamma (82115-62-6) ; Granulocyte-Macrophage Colony-Stimulating Factor (83869-56-1)
Language	English
Publishing date	2021-12-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2021.11.018
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Zs.A 1167: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Induction of a colitogenic phenotype in Th1-like cells depends on interleukin-23 receptor signaling.

Immunity

2022 Volume 55, Issue 9, Page(s) 1663–1679.e6

Abstract: Interleukin-23 receptor plays a critical role in inducing inflammation and autoimmunity. Here, we report that Th1-like cells differentiated in vitro with IL-12 + IL-21 showed similar IL-23R expression to that of pathogenic Th17 cells using eGFP reporter ... ...

Abstract	Interleukin-23 receptor plays a critical role in inducing inflammation and autoimmunity. Here, we report that Th1-like cells differentiated in vitro with IL-12 + IL-21 showed similar IL-23R expression to that of pathogenic Th17 cells using eGFP reporter mice. Fate mapping established that these cells did not transition through a Th17 cell state prior to becoming Th1-like cells, and we observed their emergence in vivo in the T cell adoptive transfer colitis model. Using IL-23R-deficient Th1-like cells, we demonstrated that IL-23R was required for the development of a highly colitogenic phenotype. Single-cell RNA sequencing analysis of intestinal T cells identified IL-23R-dependent genes in Th1-like cells that differed from those expressed in Th17 cells. The perturbation of one of these regulators (CD160) in Th1-like cells inhibited the induction of colitis. We thus uncouple IL-23R as a purely Th17 cell-specific factor and implicate IL-23R signaling as a pathogenic driver in Th1-like cells inducing tissue inflammation.
MeSH term(s)	Animals ; Colitis ; Inflammation/metabolism ; Interleukin-23/metabolism ; Mice ; Mice, Inbred C57BL ; Phenotype ; Receptors, Interleukin/genetics ; Receptors, Interleukin/metabolism ; Th1 Cells ; Th17 Cells
Chemical Substances	Interleukin-23 ; Receptors, Interleukin
Language	English
Publishing date	2022-09-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1217235-2
ISSN	1097-4180 ; 1074-7613
ISSN (online)	1097-4180
ISSN	1074-7613
DOI	10.1016/j.immuni.2022.08.007
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Zs.A 4227: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Schwann cells promote post-traumatic nerve inflammation and neuropathic pain through MHC class II.

Hartlehnert, Maike / Derksen, Angelika / Hagenacker, Tim / Kindermann, David / Schäfers, Maria / Pawlak, Mathias / Kieseier, Bernd C / Meyer Zu Horste, Gerd

Scientific reports

2017 Volume 7, Issue 1, Page(s) 12518

Abstract: The activation of T helper cells requires antigens to be exposed on the surface of antigen presenting cells (APCs) via MHC class II (MHC-II) molecules. Expression of MHC-II is generally limited to professional APCs, but other cell types can express MHC- ... ...

Abstract	The activation of T helper cells requires antigens to be exposed on the surface of antigen presenting cells (APCs) via MHC class II (MHC-II) molecules. Expression of MHC-II is generally limited to professional APCs, but other cell types can express MHC-II under inflammatory conditions. However, the importance of these conditional APCs is unknown. We and others have previously shown that Schwann cells are potentially conditional APCs, but the functional relevance of MHC-II expression by Schwann cells has not been studied in vivo. Here, we conditionally deleted the MHC-II β-chain from myelinating Schwann cells in mice and investigated how this influenced post-traumatic intraneural inflammation and neuropathic pain using the chronic constriction injury (CCI) model. We demonstrate that deletion of MHC-II in myelinating Schwann cells reduces thermal hyperalgesia and, to a lesser extent, also diminishes mechanical allodynia in CCI in female mice. This was accompanied by a reduction of intraneural CD4+ T cells and greater preservation of preferentially large-caliber axons. Activation of T helper cells by MHC-II on Schwann cells thus promotes post-traumatic axonal loss and neuropathic pain. Hence, we provide experimental evidence that Schwann cells gain antigen-presenting function in vivo and modulate local immune responses and diseases in the peripheral nerves.
MeSH term(s)	Animals ; Antigen-Presenting Cells/immunology ; Antigen-Presenting Cells/metabolism ; Constriction, Pathologic/immunology ; Constriction, Pathologic/pathology ; Disease Models, Animal ; Histocompatibility Antigens Class II/genetics ; Humans ; Hyperalgesia/immunology ; Hyperalgesia/pathology ; Inflammation/genetics ; Inflammation/metabolism ; Inflammation/pathology ; Lymphocyte Activation/immunology ; Mice ; Neuralgia/genetics ; Neuralgia/metabolism ; Neuralgia/pathology ; Peripheral Nerves/immunology ; Peripheral Nerves/pathology ; Schwann Cells/metabolism ; Schwann Cells/pathology ; Th1 Cells/immunology ; Th1 Cells/metabolism
Chemical Substances	Histocompatibility Antigens Class II
Language	English
Publishing date	2017-10-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-017-12744-2
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Article ; Online: Checkpoint Blockade Immunotherapy Induces Dynamic Changes in PD-1

Kurtulus, Sema / Madi, Asaf / Escobar, Giulia / Klapholz, Max / Nyman, Jackson / Christian, Elena / Pawlak, Mathias / Dionne, Danielle / Xia, Junrong / Rozenblatt-Rosen, Orit / Kuchroo, Vijay K / Regev, Aviv / Anderson, Ana C

Immunity

2019 Volume 50, Issue 1, Page(s) 181–194.e6

Abstract: An improved understanding of the anti-tumor ... ...

Abstract	An improved understanding of the anti-tumor CD8
MeSH term(s)	Animals ; Antibodies, Monoclonal/therapeutic use ; Antigens, Neoplasm/immunology ; CD8-Positive T-Lymphocytes/drug effects ; CD8-Positive T-Lymphocytes/immunology ; Cell Proliferation ; Hepatitis A Virus Cellular Receptor 2/antagonists & inhibitors ; Hepatocyte Nuclear Factor 1-alpha/genetics ; Hepatocyte Nuclear Factor 1-alpha/metabolism ; Humans ; Immunologic Memory/genetics ; Immunotherapy ; Lymphocytes, Tumor-Infiltrating/drug effects ; Lymphocytes, Tumor-Infiltrating/immunology ; Melanoma, Experimental ; Mice ; Mice, Inbred C57BL ; Neoplasms, Experimental/immunology ; Neoplasms, Experimental/therapy ; Programmed Cell Death 1 Receptor/antagonists & inhibitors ; T-Lymphocyte Subsets/immunology ; Transcriptome
Chemical Substances	Antibodies, Monoclonal ; Antigens, Neoplasm ; HAVCR2 protein, human ; HNF1A protein, human ; Hepatitis A Virus Cellular Receptor 2 ; Hepatocyte Nuclear Factor 1-alpha ; PDCD1 protein, human ; Programmed Cell Death 1 Receptor
Language	English
Publishing date	2019-01-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1217235-2
ISSN	1097-4180 ; 1074-7613
ISSN (online)	1097-4180
ISSN	1074-7613
DOI	10.1016/j.immuni.2018.11.014
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Article: Stem-like intestinal Th17 cells give rise to pathogenic effector T cells during autoimmunity

Schnell, Alexandra / Huang, Linglin / Singer, Meromit / Singaraju, Anvita / Barilla, Rocky M. / Regan, Brianna M.L. / Bollhagen, Alina / Thakore, Pratiksha I. / Dionne, Danielle / Delorey, Toni M. / Pawlak, Mathias / Meyer zu Horste, Gerd / Rozenblatt-Rosen, Orit / Irizarry, Rafael A. / Regev, Aviv / Kuchroo, Vijay K.

Cell. 2021 Dec. 22, v. 184, no. 26

2021

Abstract	While intestinal Th17 cells are critical for maintaining tissue homeostasis, recent studies have implicated their roles in the development of extra-intestinal autoimmune diseases including multiple sclerosis. However, the mechanisms by which tissue Th17 cells mediate these dichotomous functions remain unknown. Here, we characterized the heterogeneity, plasticity, and migratory phenotypes of tissue Th17 cells in vivo by combined fate mapping with profiling of the transcriptomes and TCR clonotypes of over 84,000 Th17 cells at homeostasis and during CNS autoimmune inflammation. Inter- and intra-organ single-cell analyses revealed a homeostatic, stem-like TCF1⁺ IL-17⁺ SLAMF6⁺ population that traffics to the intestine where it is maintained by the microbiota, providing a ready reservoir for the IL-23-driven generation of encephalitogenic GM-CSF⁺ IFN-γ⁺ CXCR6⁺ T cells. Our study defines a direct in vivo relationship between IL-17⁺ non-pathogenic and GM-CSF⁺ and IFN-γ⁺ pathogenic Th17 populations and provides a mechanism by which homeostatic intestinal Th17 cells direct extra-intestinal autoimmune disease.
Keywords	autoimmune diseases ; autoimmunity ; homeostasis ; inflammation ; intestines ; microorganisms ; migratory behavior ; sclerosis ; transcriptome
Language	English
Dates of publication	2021-1222
Size	p. 6281-6298.e23.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2021.11.018
Database	NAL-Catalogue (AGRICOLA)

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