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Antigen presentation safeguards the integrity of the hematopoietic stem cell pool (5)

Hernández-Malmierca, Pablo [VerfasserIn] 1993- ; Vonficht, Dominik [VerfasserIn] 1991- ; Schnell, Alexandra [VerfasserIn] ; [et al.]

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UID:

(DE-627)1811014615

Format: 26

ISSN: 1875-9777

Content: Hematopoietic stem and progenitor cells (HSPCs) are responsible for the production of blood and immune cells. Throughout life, HSPCs acquire oncogenic aberrations that can cause hematological cancers. Although molecular programs maintaining stem cell integrity have been identified, safety mechanisms eliminating malignant HSPCs from the stem cell pool remain poorly characterized. Here, we show that HSPCs constitutively present antigens via major histocompatibility complex class II. The presentation of immunogenic antigens, as occurring during malignant transformation, triggers bidirectional interactions between HSPCs and antigen-specific CD4+ T cells, causing stem cell proliferation, differentiation, and specific exhaustion of aberrant HSPCs. This immunosurveillance mechanism effectively eliminates transformed HSPCs from the hematopoietic system, thereby preventing leukemia onset. Together, our data reveal a bidirectional interaction between HSPCs and CD4+ T cells, demonstrating that HSPCs are not only passive receivers of immunological signals but also actively engage in adaptive immune responses to safeguard the integrity of the stem cell pool.

Note: Gesehen am 20.07.2022

In: Cell stem cell, Amsterdam [u.a.] : Elsevier, 2007, 29(2022), 5, Seite 760-775.e10, 1875-9777

In: volume:29

In: year:2022

In: number:5

In: pages:760-775.e10

In: extent:26

Language: English

DOI: 10.1016/j.stem.2022.04.007

URL: Volltext (lizenzpflichtig)

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The BAF complex interacts with Pax6 in adult neural progenitors to establish a neurogenic cross-regulatory transcriptional network (8)

Ninković, Jovica [VerfasserIn] 1976- ; Steiner-Mezzadri, Andrea [VerfasserIn] ; Jawerka, Melanie [VerfasserIn] ; [et al.]

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UID:

(DE-627)1779080034

Format: 16

ISSN: 1875-9777

Content: Numerous transcriptional regulators of neurogenesis have been identified in the developing and adult brain, but how neurogenic fate is programmed at the epigenetic level remains poorly defined. Here, we report that the transcription factor Pax6 directly interacts with the Brg1-containing BAF complex in adult neural progenitors. Deletion of either Brg1 or Pax6 in the subependymal zone (SEZ) causes the progeny of adult neural stem cells to convert to the ependymal lineage within the SEZ while migrating neuroblasts convert to different glial lineages en route to or in the olfactory bulb (OB). Genome-wide analyses reveal that the majority of genes downregulated in the Brg1 null SEZ and OB contain Pax6 binding sites and are also downregulated in Pax6 null SEZ and OB. Downstream of the Pax6-BAF complex, we find that Sox11, Nfib, and Pou3f4 form a transcriptional cross-regulatory network that drives neurogenesis and can convert postnatal glia into neurons. Taken together, elements of our work identify a tripartite effector network activated by Pax6-BAF that programs neuronal fate.

Note: Gesehen am 25.11.2021

In: Cell stem cell, Amsterdam [u.a.] : Elsevier, 2007, 13(2013), 4, Seite 403-418, 1875-9777

In: volume:13

In: year:2013

In: number:4

In: pages:403-418

In: extent:16

Language: English

DOI: 10.1016/j.stem.2013.07.002

URL: Volltext (lizenzpflichtig)

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Cell stem cell (from 2007)

Cambridge, Mass. : Cell Press ; 1.2007,1(Juli) -

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UID:

(DE-627)535183828

ISSN: 1934-5909

Additional Edition: 1875-9777

Additional Edition: Online-Ausg. Cell stem cell Amsterdam [u.a.] : Elsevier, 2007 1875-9777

Language: English

Keywords: Zeitschrift

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Cell stem cell (2007)

Amsterdam [u.a.] : Elsevier ; 1.2007 -

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UID:

(DE-627)535183836

Format: Online-Ressource

ISSN: 1875-9777

Note: Gesehen am 19.09.12

Additional Edition: 1934-5909

Additional Edition: Erscheint auch als Druck-Ausgabe Cell stem cell Cambridge, Mass. : Cell Press, 2007 1934-5909

Language: English

Keywords: Stammzelle ; Zeitschrift

URL: teilw. kostenfrei

URL: https://ezb.ur.de/?2375356-0

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The chromatin remodeler CHD7 regulates adult neurogenesis via activation of SoxC transcription factors (3)

Feng, Weijun [VerfasserIn] ; Khan, Muhammad Amir [VerfasserIn] 1977- ; Bellvís Zambrano, Pablo [VerfasserIn] ; [et al.]

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UID:

(DE-627)1751222144

Format: 11

ISSN: 1875-9777

Content: Chromatin factors that regulate neurogenesis in the central nervous system remain to be explored. Here, we demonstrate that the chromatin remodeler chromodomain-helicase-DNA-binding protein 7 (CHD7), a protein frequently mutated in human CHARGE syndrome, is a master regulator of neurogenesis in mammalian brain. CHD7 is selectively expressed in actively dividing neural stem cells (NSCs) and progenitors. Genetic inactivation of CHD7 in NSCs leads to a reduction of neuronal differentiation and aberrant dendritic development of newborn neurons. Strikingly, physical exercise can rescue the CHD7 mutant phenotype in the adult hippocampal dentate gyrus. We further show that in NSCs, CHD7 stimulates the expression of Sox4 and Sox11 genes via remodeling their promoters to an open chromatin state. Our study demonstrates an essential role of CHD7 in activation of the neuronal differentiation program in NSCs, thus providing insights into epigenetic regulation of stem cell differentiation and molecular mechanism of human CHARGE syndrome.

Note: Gesehen am 12.03.2021

In: Cell stem cell, Amsterdam [u.a.] : Elsevier, 2007, 13(2013), 1, Seite 62-72, 1875-9777

In: volume:13

In: year:2013

In: number:1

In: pages:62-72

In: extent:11

Language: English

DOI: 10.1016/j.stem.2013.05.002

URL: Volltext (lizenzpflichtig)

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Clonally resolved single-cell multi-omics identifies routes of cellular differentiation in acute myeloid leukemia (4)

Beneyto Calabuig, Sergi [VerfasserIn] ; Merbach, Anne Kathrin [VerfasserIn] ; Kniffka, Jonas-Alexander [VerfasserIn] ; [et al.]

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UID:

(DE-627)1852476796

Format: 25 , Diagramme, Illustrationen

ISSN: 1875-9777

Content: acute myeloid leukemia, leukemic stem cells, cancer stem cells, hematopoietic stem cells, cellular differentiation, AML, LSC, CSC, HSC, single-cell RNA-seq, computational biology, single-cell genomics, single-cell transcriptomics, computational method

Note: Online verfügbar: 24. April 2023, Artikelversion: 4. Mai 2023

In: Cell stem cell, Amsterdam [u.a.] : Elsevier, 2007, 30(2023), 5 vom: Mai, Seite 706-721.e8, 1875-9777

In: volume:30

In: year:2023

In: number:5

In: month:05

In: pages:706-721.e8

In: extent:25

Language: English

DOI: 10.1016/j.stem.2023.04.001

DOI: 10.25673/108982

URL: kostenfrei

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Coordinated changes in cellular behavior ensure the lifelong maintenance of the hippocampal stem cell population (12)

Harris, Lachlan [VerfasserIn] ; Rigo, Piero [VerfasserIn] ; Stiehl, Thomas [VerfasserIn] ; [et al.]

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UID:

(DE-627)1794001190

Format: 20

ISSN: 1875-9777

Content: Neural stem cell numbers fall rapidly in the hippocampus of juvenile mice but stabilize during adulthood, ensuring lifelong hippocampal neurogenesis. We show that this stabilization of stem cell numbers in young adults is the result of coordinated changes in stem cell behavior. Although proliferating neural stem cells in juveniles differentiate rapidly, they increasingly return to a resting state of shallow quiescence and progress through additional self-renewing divisions in adulthood. Single-cell transcriptomics, modeling, and label retention analyses indicate that resting cells have a higher activation rate and greater contribution to neurogenesis than dormant cells, which have not left quiescence. These changes in stem cell behavior result from a progressive reduction in expression of the pro-activation protein ASCL1 because of increased post-translational degradation. These cellular mechanisms help reconcile current contradictory models of hippocampal neural stem cell (NSC) dynamics and may contribute to the different rates of decline of hippocampal neurogenesis in mammalian species, including humans.

Note: Gesehen am 28.02.2022

In: Cell stem cell, Amsterdam [u.a.] : Elsevier, 2007, 28(2021), 5 vom: 6. Mai, Seite 863-876,e1-e6, 1875-9777

In: volume:28

In: year:2021

In: number:5

In: day:6

In: month:05

In: pages:863-876,e1-e6

In: extent:20

Language: English

DOI: 10.1016/j.stem.2021.01.003

URL: Volltext (lizenzpflichtig)

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Diazepam binding inhibitor promotes progenitor proliferation in the postnatal SVZ by reducing GABA signaling (5)

Alfonso, Julieta [VerfasserIn] ; Le Magueresse, Corentin [VerfasserIn] ; Zuccotti, Annalisa [VerfasserIn] 1983- ; [et al.]

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UID:

(DE-627)1572316179

Format: 12

ISSN: 1875-9777

Content: The subventricular zone (SVZ) of the lateral ventricles is the largest neurogenic niche of the postnatal brain. New SVZ-generated neurons migrate via the rostral migratory stream to the olfactory bulb (OB) where they functionally integrate into preexisting neuronal circuits. Nonsynaptic GABA signaling was previously shown to inhibit SVZ-derived neurogenesis. Here we identify the endogenous protein diazepam binding inhibitor (DBI) as a positive modulator of SVZ postnatal neurogenesis by regulating GABA activity in transit-amplifying cells. We performed DBI loss- and gain-of-function experiments in vivo at the peak of postnatal OB neuron generation in mice and demonstrate that DBI enhances proliferation by preventing SVZ progenitors to exit the cell cycle. Furthermore, we provide evidence that DBI exerts its effect on SVZ progenitors via its octadecaneuropeptide proteolytic product (ODN) by inhibiting GABA-induced currents. Together our data reveal a regulatory mechanism by which DBI counteracts the inhibitory effect of nonsynaptic GABA signaling on subventricular neuronal proliferation.

Note: Gesehen am 24.04.2018

In: Cell stem cell, Amsterdam [u.a.] : Elsevier, 2007, 10(2012), 1, Seite 76-87, 1875-9777

In: volume:10

In: year:2012

In: number:1

In: pages:76-87

In: extent:12

Language: English

DOI: 10.1016/j.stem.2011.11.011

URL: Volltext (kostenfrei)

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Differential alternative polyadenylation landscapes mediate hematopoietic stem cell activation and regulate glutamine metabolism (30)

Sommerkamp, Pia [VerfasserIn] ; Altamura, Sandro [VerfasserIn] ; Renders, Simon [VerfasserIn] ; [et al.]

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UID:

(DE-627)1694097943

Format: 17

ISSN: 1875-9777

Content: Alternative polyadenylation (APA) is emerging as an important regulatory mechanism of RNA and protein isoform expression by controlling 3′ untranslated region (3′-UTR) composition. The relevance of APA in stem cell hierarchies remains elusive. Here, we first demonstrate the requirement of the APA regulator Pabpn1 for hematopoietic stem cell (HSC) function. We then determine the genome-wide APA landscape (APAome) of HSCs and progenitors by performing low-input 3′ sequencing paired with bioinformatic pipelines. This reveals transcriptome-wide dynamic APA patterns and an overall shortening of 3′-UTRs during differentiation and upon homeostatic or stress-induced transition from quiescence to proliferation. Specifically, we show that APA regulates activation-induced Glutaminase (Gls) isoform switching by Nudt21. This adaptation of the glutamine metabolism by increasing the GAC:KGA isoform ratio fuels versatile metabolic pathways necessary for HSC self-renewal and proper stress response. Our study establishes APA as a critical regulatory layer orchestrating HSC self-renewal, behavior, and commitment.

Note: Gesehen am 06.04.2020

In: Cell stem cell, Amsterdam [u.a.] : Elsevier, 2007, 26(2020), 5, Seite 722-738.e7, 1875-9777

In: volume:26

In: year:2020

In: number:5

In: pages:722-738.e7

In: extent:17

Language: English

DOI: 10.1016/j.stem.2020.03.003

URL: Volltext (lizenzpflichtig)

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Distinct types of tumor-initiating cells form human colon cancer tumors and metastases (7)

Dieter, Sebastian M. [VerfasserIn] 1983- ; Ball, Claudia R. [VerfasserIn] ; Hoffmann, Christopher M. [VerfasserIn] ; [et al.]

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UID:

(DE-627)1806777657

Format: 9

ISSN: 1875-9777

Content: Human colon cancer harbors a small subfraction of tumor-initiating cells (TICs) that is assumed to be a functionally homogeneous stem-cell-like population driving tumor maintenance and metastasis formation. We found unexpected cellular heterogeneity within the TIC compartment, which contains three types of TICs. Extensively self-renewing long-term TICs (LT-TICs) maintained tumor formation in serial xenotransplants. Tumor transient amplifying cells (T-TACs) with limited or no self-renewal capacity contributed to tumor formation only in primary mice. Rare delayed contributing TICs (DC-TICs) were exclusively active in secondary or tertiary mice. Bone marrow was identified as an important reservoir of LT-TICs. Metastasis formation was almost exclusively driven by self-renewing LT-TICs. Our results demonstrate that tumor initiation, self-renewal, and metastasis formation are limited to particular subpopulations of TICs in primary human colon cancer. We identify LT-TICs as a quantifiable target for therapies aimed toward eradication of self-renewing tumorigenic and metastatic colon cancer cells.

Note: Gesehen am 10.06.2022

In: Cell stem cell, Amsterdam [u.a.] : Elsevier, 2007, 9(2011), 4, Seite 357-365, 1875-9777

In: volume:9

In: year:2011

In: number:4

In: pages:357-365

In: extent:9

Language: English

DOI: 10.1016/j.stem.2011.08.010

URL: Volltext (lizenzpflichtig)

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Kooperativer Bibliotheksverbund

Berlin Brandenburg