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A tunable human intestinal organoid system achieves controlled balance between self-renewal and differentiation.
Nat Commun
January 2025
Institute for Regenerative Medicine, State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.
A balance between stem cell self-renewal and differentiation is required to maintain concurrent proliferation and cellular diversification in organoids; however, this has proven difficult in homogeneous cultures devoid of in vivo spatial niche gradients for adult stem cell-derived organoids. In this study, we leverage a combination of small molecule pathway modulators to enhance the stemness of organoid stem cells, thereby amplifying their differentiation potential and subsequently increasing cellular diversity within human intestinal organoids without the need for artificial spatial or temporal signaling gradients. Moreover, we demonstrate that this balance between self-renewal and differentiation can be effectively and reversibly shifted from secretory cell differentiation to the enterocyte lineage with enhanced proliferation using BET inhibitors, or unidirectional differentiation towards specific intestinal cell types by manipulating in vivo niche signals such as Wnt, Notch, and BMP.
View Article and Find Full Text PDFDynamic and photodegradable dextran/gelatin hydrogel niche crosslinked with disulfide bonds: Promoting growth and release of stem cells.
Int J Biol Macromol
December 2024
School of Basic Medical Sciences, North China University of Science and Technology, Tangshan 063210, China. Electronic address:
Due to the utilization of well-defined artificial niches, stem cell culture in a three-dimensional hydrogel matrix has been a promising method for obtaining sufficient seed cells. Although various hydrogels can support desirable cell proliferation, establishing a normalized hydrogel that adequately mimics the extracellular matrix (ECM), maintains stemness and allows for controlled release of stem cells remains a significant challenge. Herein, we report a hydrogel composed of sulfobetaine-modified dextran and gelatin to maintain stemness and enable the rapid release of adipose-derived stem cells (ADSCs).
View Article and Find Full Text PDFThe effector PieF modulates mRNA stability through association with eukaryotic CCR4-NOT.
mSphere
December 2024
Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Unlabelled: The eukaryotic CCR4-NOT deadenylase complex is a highly conserved regulator of mRNA metabolism that influences the expression of the complete transcriptome, representing a prime target for a generalist bacterial pathogen. We show that a translocated bacterial effector protein, PieF (Lpg1972) of , directly interacts with the CNOT7/8 nuclease module of CCR4-NOT, with a dissociation constant in the low nanomolar range. PieF is a robust inhibitor of the DEDD-type nuclease, CNOT7, acting in a stoichiometric, dose-dependent manner.
View Article and Find Full Text PDFThe functional dominance and metabolic diversity of comammox Nitrospira in recirculating aquaculture systems.
Water Res
December 2024
Australian Centre for Water and Environmental Biotechnology, The University of Queensland, St. Lucia, Brisbane, QLD 4072, Australia.
As a newly discovered group of ammonia-oxidizing microorganisms, complete ammonia oxidizing (comammox) Nitrospira has been widely found in various oligotrophic ecosystems. However, their activity and ecological niche is still unclear in recirculating aquaculture systems (RAS). This study aimed to compare the abundance and activity of comammox Nitrospira, ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA), and elucidate metabolic versatility of comammox Nitrospira in RAS.
View Article and Find Full Text PDFExploring the effects of culture conditions on Yapsin () gene expression in .
Open Life Sci
November 2024
Department of Comparative Biochemistry and Bioanalytics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387, Kraków, Poland.
, previously known as , has the great potential to cause systemic fungal infections despite its similarity to baker's yeast. Its pathogenicity is attributed to the production of numerous virulence factors, among which the genes (-) encoding aspartyl proteases have yet to be sufficiently characterized, and limited studies suggest their involvement in cellular homeostasis. The study's novelty is an investigation of the role of in ability to adapt to different host environments.
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