Article
Hematology
Valentina Vavassori, Samuele Ferrari, Stefano Beretta, Claudia Asperti, Luisa Albano, Andrea Annoni, Chiara Gaddoni, Angelica Varesi, Monica Soldi, Alessandro Cuomo, Tiziana Bonaldi, Marina Radrizzani, Ivan Merelli, Luigi Naldini
Summary: Ex vivo gene editing in T cells and HSPCs can be improved by using lipid nanoparticles for RNA delivery, which reduces cell death and improves cell growth, leading to better editing efficiency.
Review
Cell Biology
Stefania Crippa, Ludovica Santi, Margherita Berti, Giada De Ponti, Maria Ester Bernardo
Summary: The human organism requires the production of approximately 1 trillion new blood cells per day through hematopoiesis in the bone marrow, regulated by the BM microenvironment and HSPCs. The BM niche, defined by interactions between HSPCs and non-hematopoietic cells, controls HSPC maintenance and orchestrates hematopoiesis according to the body's needs. Mesenchymal stromal cells (MSCs) play a key role in the BM niche by regulating HSPC homeostasis and impacting the outcome of hematopoietic stem cell transplantation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biology
Anders Laustsen, Renee M. Van der Sluis, Albert Gris-Oliver, Sabina Sanchez Hernandez, Ena Cemalovic, Hai Q. Tang, Lars Henning Pedersen, Niels Uldbjerg, Martin R. Jakobsen, Rasmus O. Bak
Summary: Researchers have developed a new method for generating pDCs from whole blood, and these cells exhibit the characteristics and functions of pDCs. While TLR7/9 responses significantly decrease when cultured under GMP standards, this can be rescued by adding ascorbic acid.
Article
Oncology
Yuan Wang, Ryohichi Sugimura
Summary: Hematopoietic stem cells (HSCs) are promising for treating various hereditary and hematologic diseases by differentiating into mature blood cells. However, the low population of HSCs in cord blood and bone marrow has led to investigations on ex vivo HSC expansion. This review surveys the current techniques for HSC self-renewal and summarizes the effects of intrinsic and extrinsic factors on HSC expansion, as well as the challenges and opportunities in this field.
EXPERIMENTAL CELL RESEARCH
(2023)
Article
Cell Biology
Vashe Chandrakanthan, Prunella Rorimpandey, Fabio Zanini, Diego Chacon, Jake Olivier, Swapna Joshi, Young Chan Kang, Kathy Knezevic, Yizhou Huang, Qiao Qiao, Rema A. Oliver, Ashwin Unnikrishnan, Daniel R. Carter, Brendan Lee, Chris Brownlee, Carl Power, Robert Brink, Simon Mendez-Ferrer, Grigori Enikolopov, William Walsh, Berthold Gottgens, Samir Taoudi, Dominik Beck, John E. Pimanda
Summary: Chandrakanthan et al. have identified Mesp1-derived PDGFRA(+) stromal cells as aortic endothelial precursor cells that regulate the generation of long-term hematopoietic stem cells during development. This study provides a new potential tool for generating engraftable hematopoietic stem cells.
NATURE CELL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Sanshiro Kanazawa, Hiroyuki Okada, Dan Riu, Yo Mabuchi, Chihiro Akazawa, Junichi Iwata, Kazuto Hoshi, Atsuhiko Hikita
Summary: This study demonstrates the important role of c-Mpl signal in the proliferation and differentiation ability of mesenchymal stem cells (MSCs), which are maintained through co-culture with hematopoietic stem cells (HSCs). Furthermore, the study suggests the existence of a hematopoietic-mesenchymal signal and highlights the significance of HSC state in the stability of MSC properties.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Jie Yang, Guanghui Shen, Jun Cao, Jinlan Zhang, Yunqing Gu, Xinyu Zhang, Xiaoyi Jiang, Min Luo, Zhigang Lu
Summary: Membrane anchored Angptl2 shows higher activities in activating LILRB2 and expanding HSCs compared to soluble protein.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Review
Cell Biology
Soudeh Ghafouri-Fard, Vahid Niazi, Mohammad Taheri, Abbas Basiri
Summary: Hematopoietic stem cells play a crucial role in both preserving the blood system and potentially differentiating into non-hematopoietic cells for the treatment of human disorders.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Christelle Debeissat, Maryse Avalon, Mathilde Huart, Pascale Duchez, Laura Rodriguez, Marija Vlaski-Lafarge, Zoran Ivanovic, Philippe Brunet de la Grange
Summary: Alpha lipoic acid (ALA) enhances ex vivo expansion of CD34 positive cells in peripheral blood, resulting in increased expansion of primitive cells and decreased expansion of differentiated cells. Moreover, ALA improves the redox status of hematopoietic cells.
Article
Biology
Eva M. Fast, Audrey Sporrij, Margot Manning, Edroaldo Lummertz Rocha, Song Yang, Yi Zhou, Jimin Guo, Ninib Baryawno, Nikolaos Barkas, David Scadden, Fernando Camargo, Leonard Zon
Summary: The article discusses the functions of adult stem cells and the effects of external signalling molecules on stem cells. The study reveals the rapid response of stem cells to external signals, with unique gene expression patterns affected by different chemicals. The results suggest that stem cells may be primed by low levels of external signalling molecules released from their microenvironment to better respond to future stress or injuries.
Article
Cell & Tissue Engineering
Koki Kimura, Shiori Yamamori, Masaharu Hazawa, Jingjing Kobayashi-Sun, Mao Kondo, Richard W. Wong, Isao Kobayashi
Summary: Using a stromal cell line from the zebrafish kidney, researchers found that an inhibitor of canonical Wnt signaling, IWR-1-endo, is a potent regulator of hematopoietic stem cells (HSCs). The stromal cells weakly expressed HSC maintenance factors but highly expressed canonical Wnt ligand genes. Adding IWR-1-endo or inhibiting canonical Wnt signaling increased the number of HSCs.
Article
Cell Biology
Chao-Ling Yao, Poyin Huang, Tsai-Chi Liu, Yung-Kai Lin, Ching-Yun Chen, Yi-Ting Lai, Tzu Yun Chin, Tsung-Yu Tseng, Yi-Chiung Hsu
Summary: Different experimental strategies for ex vivo expansion of human hematopoietic stem cells (HSCs) have been developed, however, the genomic function of expanded HSCs under different culture systems remains unclear. This study compared gene expression profiles of HSCs in serum and serum-free culture systems, identifying differentially expressed genes enriched in the TNF-regulated inflammatory pathway in the FBS culture system. The ex vivo expansion of HSCs using the FBS culture system induces an inflammatory response and high CD38 expression, providing new insights into genomic functions of HSCs under different expanded cultures.
Article
Medicine, Research & Experimental
L. B. Buravkova, M. Ezdakova, I. Andrianova, A. N. Gornostaeva, P. Bobyleva, E. R. Andreeva
Summary: The study demonstrated that during ex vivo expansion, cord blood hematopoietic stem progenitor cells (cbHSPCs) can influence the functional state of mesenchymal stromal cells (MSCs), leading to the formation of early stromal progenitors with a bipotential osteo-adipogenic profile. The joint coculture resulted in a specific hematopoiesis-supportive environment, with the expression of certain MSC genes upregulated and a balance of myeloid regulators maintained. Short-term osteoinduction prior to coculture enhanced the development of a bipotential profile, indicating a more committed state of cbHSPCs.
Article
Cell & Tissue Engineering
Valentina Orticelli, Andrea Papait, Elsa Vertua, Patrizia Bonassi Signoroni, Pietro Romele, Lorena Di Pietro, Marta Magatti, Luciana Teofili, Antonietta Rosa Silini, Ornella Parolini
Summary: This study investigated the potential of human term placenta-derived amniotic membrane MSCs (hAMSC) to support the ex vivo expansion of HSC and progenitor cells. The results suggest that hAMSCs are a valuable alternative to BM-MSC for enhancing the proliferation and maintaining stemness of CB-HSC, and can improve the colony forming unit ability and long-term culture initiating cells ability, addressing the need for high HSC content in CB units available for transplantation.
STEM CELLS TRANSLATIONAL MEDICINE
(2021)
Article
Medicine, Research & Experimental
Nopmullee Tanhuad, Umnuaychoke Thongsa-Ad, Nareerat Sutjarit, Ploychompoo Yoosabai, Wittaya Panvongsa, Sirapope Wongniam, Apichart Suksamrarn, Pawinee Piyachaturawat, Usanarat Anurathapan, Suparerk Borwornpinyo, Arthit Chairoungdua, Suradej Hongeng, Kanit Bhukhai
Summary: The use of ASPP 049 has been shown to significantly increase the number of adult CD34+ cells and improve their functional properties, thus enhancing the ex vivo culture of hematopoietic stem cells.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Review
Hematology
Chris S. Vink, Elaine Dzierzak
Summary: This review article discusses the establishment of the adult-definitive hematopoietic hierarchy and hematopoietic stem cells (HSCs) during embryonic development, with a focus on the formation of intra-aortic/arterial hematopoietic clusters (IAHCs) in various mammals. The IAHC cells arise through an endothelial-to-hematopoietic transition and exhibit characteristics of both endothelial and hematopoietic cells. The article explores the current state of knowledge on IAHC cells, including markers for their isolation and characterization, and speculates on the function of uncharacterized IAHC cells.
EXPERIMENTAL HEMATOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Ruben Boers, Joachim Boers, Beatrice Tan, Marieke E. van Leeuwen, Evelyne Wassenaar, Erlantz Gonzalez Sanchez, Esther Sleddens, Yasha Tenhagen, Eskeatnaf Mulugeta, Joop Laven, Menno Creyghton, Willy Baarends, Wilfred F. J. van IJcken, Joost Gribnau
Summary: In this study, a bacterial methylation mark was used to label transcribed genes and active enhancers, allowing for tracking of cell state changes. This technique revealed rapid and coordinated activation of enhancers and nearby genes during enterocyte differentiation in the intestine. Furthermore, it provided insights into the chromatin landscape of intestinal stem cells and their differentiation process.
NATURE BIOTECHNOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Delilah Hendriks, Jos F. Brouwers, Karien Hamer, Maarten H. Geurts, Lea Luciana, Simone Massalini, Carmen Lopez-Iglesias, Peter J. Peters, Maria J. Rodriguez-Colman, Susana Chuva de Sousa Lopes, Benedetta Artegiani, Hans Clevers
Summary: Organoid models of early liver disease, such as nonalcoholic fatty liver disease (NAFLD), are valuable for target discovery and drug screening. Using human fetal hepatocyte organoids, the first stage of NAFLD, steatosis, was successfully modeled with various triggers. Screening of drug candidates identified compounds that effectively resolved steatosis by repressing de novo lipogenesis. The study also introduced FatTracer, a CRISPR screening platform, to identify steatosis modulators and potential targets.
NATURE BIOTECHNOLOGY
(2023)
Article
Multidisciplinary Sciences
Nannan Guo, Na Li, Li Jia, Qinyue Jiang, Mette Schreurs, Vincent van Unen, Susana M. Chuva de Sousa Lopes, Alexandra A. Vloemans, Jeroen Eggermont, Boudewijn Lelieveldt, Frank J. T. Staal, Noel F. C. C. de Miranda, M. Fernanda Pascutti, Frits Koning
Summary: This study reveals the changes in immune subsets in the developing human foetal intestine, showing the sequential appearance of different types of immune cells between gestational weeks 14 and 22. The presence of immune subset-committed cells capable of local proliferation suggests their important role in the development of organized immune structures and potential influence on microbial colonization after birth.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Laura Ruland, Francesco Andreatta, Simone Massalini, Susana Chuva de Sousa Lopes, Hans Clevers, Delilah Hendriks, Benedetta Artegiani
Summary: By engineering human organoids to reflect different genetic backgrounds of fibrolamellar carcinoma (FLC), the authors demonstrate that hepatocytes can be a cell-of-origin of FLC that transdifferentiate into ductal/progenitor like cells due to combined BAP1 and PRKAR2A loss.
NATURE COMMUNICATIONS
(2023)
Review
Oncology
Sara Vasconcelos, Carla Canicais, Susana M. Chuva de Sousa Lopes, C. Joana Marques, Sofia Doria
Summary: The placenta is crucial for mammalian embryo and fetal development. Understanding the role of epigenetics, including DNA hydroxymethylation, in placental development and function can help improve diagnosis and treatment of obstetric complications. This review focuses on DNA hydroxymethylation and its regulators in both human and mouse placenta, along with its relevance to genomic imprinting and pregnancy complications such as intrauterine growth restriction, preeclampsia, and pregnancy loss. The findings suggest that DNA hydroxymethylation plays a dynamic role in trophoblast cell differentiation during gestation and may be an important factor in gene expression regulation in the placenta.
CLINICAL EPIGENETICS
(2023)
Review
Multidisciplinary Sciences
Varsha Jain, Susana M. Chuva de Sousa M. Lopes, Mohammed A. Benotmane, Vittore Verratti, Rod T. Mitchell, Jan-Bernd Stukenborg
Summary: This review summarises key aspects of the first reproductive and developmental systems Science Community White Paper, supported by the European Space Agency (ESA). The white papers aim to reflect on the implications of space travel on the male and female reproductive systems and explore how this may impact society on Earth.
Article
Biochemistry & Molecular Biology
Iris J. M. Levink, Maurice P. H. M. Jansen, Zakia Azmani, Wilfred van IJcken, Ronald van Marion, Maikel P. Peppelenbosch, Djuna L. Cahen, Gwenny M. Fuhler, Marco J. Bruno
Summary: Molecular profiling may aid in earlier detection and personalized treatment of pancreatic cancer. This study found higher cfDNA concentration in pancreatic juice (PJ) than in plasma, but similar mutation detection rates, suggesting the need for further research on the suitability of plasma and PJ for early PC detection.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biotechnology & Applied Microbiology
Bieke Bekaert, Annekatrien Boel, Lisa De Witte, Winter Vandenberghe, Mina Popovic, Panagiotis Stamatiadis, Gwenny Cosemans, Lise Tordeurs, Athina-Maria De Loore, Susana Marina Chuva de Sousa Lopes, Petra De Sutter, Dominic Stoop, Paul Coucke, Bjoern Menten, Bjoern Heindryckx
Summary: Gene correction using targeted nucleases in human embryos shows potential to reduce mutation transmission, but concerns have been raised about mosaicism and loss of heterozygosity observed in CRISPR-Cas9-targeted embryos. In this study, researchers successfully corrected a basepair substitution in PLCZ1 gene related to infertility in some embryos, but also observed short-range loss of heterozygosity. These findings contribute to the ongoing discussion about double-strand break repair mechanisms in early human embryos.
Article
Multidisciplinary Sciences
Annie S. P. Yang, Devanjali Dutta, Kai Kretzschmar, Delilah Hendriks, Jens Puschhof, Huili Hu, Kim E. Boonekamp, Youri van Waardenburg, Susana M. Chuva de Sousa Lopes, Geert-Jan van Gemert, Johannes H. W. de Wilt, Teun Bousema, Hans Clevers, Robert W. Sauerwein
Summary: Researchers have found that hepatocytes derived from human hepatocyte organoids (HepOrgs) can support the development of Plasmodium falciparum, and have identified the importance of the host factor scavenger receptor B1 (SRB1) in parasite development.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Elisabeth M. Jongbloed, Maurice P. H. M. Jansen, Vanja de Weerd, Jean A. Helmijr, Corine M. Beaufort, Marcel J. T. Reinders, Ronald van Marion, Wilfred F. J. van IJcken, Gabe S. Sonke, Inge R. Konings, Agnes Jager, John W. M. Martens, Saskia M. Wilting, Stavros Makrodimitris
Summary: Next generation sequencing of cfDNA is a promising method for treatment monitoring and therapy selection in MBC. However, distinguishing tumor-specific variants from sequencing artefacts and germline variation is challenging. To address this, a machine learning model was built to remove false positive variant calls and select tumor-derived variants.
SCIENTIFIC REPORTS
(2023)
Review
Biotechnology & Applied Microbiology
Julieta S. Del Valle, Susana Chuva de Sousa M. Lopes
Summary: Ovarian dysfunction has significant consequences for female health, including infertility and conditions such as osteoporosis and cardiovascular disease. The development of bioengineered three-dimensional (3D) ovarian models provides a valuable tool for studying ovarian physiology and pathology, as well as potential alternatives for fertility preservation and restoration of ovarian function. This review focuses on the latest advances in 3D ovarian platforms, including modeling female reproduction, physiology, ovarian cancer, and drug screening.
BIOENGINEERING-BASEL
(2023)
Article
Genetics & Heredity
Stavroula Siamoglou, Ruben Boers, Maria Koromina, Joachim Boers, Anna Tsironi, Theodora Chatzilygeroudi, Vasileios Lazaris, Evgenia Verigou, Alexandra Kourakli, Wilfred F. J. van IJcken, Joost Gribnau, Argiris Symeonidis, George P. Patrinos
Summary: Myelodysplastic syndromes (MDS) are a group of hematological malignancies characterized by ineffective hematopoiesis, cytogenetic abnormalities, and a high risk of transformation to acute myeloid leukemia (AML). This study used methylated DNA sequencing (MeD-seq) to identify potential epigenomic targets associated with MDS subtypes. The results identified differentially methylated CpG islands, transcription start sites, and post-transcriptional start sites within the PCDHG and ZNF gene families. These findings provide important insights into the epigenomic component of MDS pathogenesis and the potential for targeted drug treatment.
Article
Cell Biology
Chris S. Vink, Anna Popravko, Elaine Dzierzak
Summary: This article discusses the early development of the hematopoietic system and the formation of stem cells. It explores the heterogeneity and stability issues in the transcriptional program of hematopoietic cells.
CURRENT OPINION IN CELL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Amy C. J. van der List, Nicolle H. R. Litjens, Rutger W. W. Brouwer, Mariska Klepper, Alexander T. den Dekker, Wilfred F. J. van Ijcken, Michiel G. H. Betjes
Summary: After kidney transplantation, recipient T cells develop low responsiveness to donor-specific antigens over time. Apoptosis was identified as a possible underlying mechanism. This study investigated the genetic and receptor profiles of individual alloreactive T cells from kidney transplant recipients using single-cell RNA sequencing. The findings suggest that post-transplantation, donor-reactive CD4+ T cell clones preferentially undergo apoptosis in stable kidney transplant recipients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
