{"entity": "journal", "iuid": "8631dd1d0cec44e78d2f48a8966df20f", "timestamp": "2026-07-17T08:17:28.156Z", "links": {"self": {"href": "https://publications.scilifelab.se/journal/Stem%20Cell%20Reports.json"}, "display": {"href": "https://publications.scilifelab.se/journal/Stem%20Cell%20Reports"}}, "title": "Stem Cell Reports", "issn": "2213-6711", "issn-l": "2213-6711", "publications_count": 8, "publications": [{"entity": "publication", "iuid": "f63e36a5ea3a42329893558a0caec322", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f63e36a5ea3a42329893558a0caec322.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f63e36a5ea3a42329893558a0caec322"}}, "title": "Single-cell transcriptomics reveals correct developmental dynamics and high-quality midbrain cell types by improved hESC differentiation.", "authors": [{"family": "Nishimura", "given": "Kaneyasu", "initials": "K"}, {"family": "Yang", "given": "Shanzheng", "initials": "S"}, {"family": "Lee", "given": "Ka Wai", "initials": "KW"}, {"family": "\u00c1sgr\u00edmsd\u00f3ttir", "given": "Emil\u00eda Sif", "initials": "ES"}, {"family": "Nikouei", "given": "Kasra", "initials": "K"}, {"family": "Paslawski", "given": "Wojciech", "initials": "W"}, {"family": "Gnodde", "given": "Sabine", "initials": "S"}, {"family": "Lyu", "given": "Guochang", "initials": "G"}, {"family": "Hu", "given": "Lijuan", "initials": "L"}, {"family": "Salt\u00f3", "given": "Carmen", "initials": "C"}, {"family": "Svenningsson", "given": "Per", "initials": "P"}, {"family": "Hjerling-Leffler", "given": "Jens", "initials": "J"}, {"family": "Linnarsson", "given": "Sten", "initials": "S"}, {"family": "Arenas", "given": "Ernest", "initials": "E"}], "type": "journal article", "published": "2023-01-10", "journal": {"title": "Stem Cell Reports", "issn": "2213-6711", "issn-l": "2213-6711", "volume": "18", "issue": "1", "pages": "337-353"}, "abstract": "Stem cell technologies provide new opportunities for modeling cells in health and disease and for regenerative medicine. In both cases, developmental knowledge and defining the molecular properties and quality of the cell types is essential. In this study, we identify developmental factors important for the differentiation of human embryonic stem cells (hESCs) into functional midbrain dopaminergic (mDA) neurons. We found that laminin-511, and dual canonical and non-canonical WNT activation followed by GSK3\u03b2 inhibition plus FGF8b, improved midbrain patterning. In addition, neurogenesis and differentiation were enhanced by activation of liver X receptors and inhibition of fibroblast growth factor signaling. Moreover, single-cell RNA-sequencing analysis revealed a developmental dynamics similar to that of the endogenous human ventral midbrain and the emergence of high-quality molecularly defined midbrain cell types, including mDA neurons. Our study identifies novel factors important for human midbrain development and opens the door for a future application of molecularly defined hESC-derived cell types in Parkinson disease.", "doi": "10.1016/j.stemcr.2022.10.016", "pmid": "36400027", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Production)": "Service", "NGI Short read": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9860082"}, {"db": "pii", "key": "S2213-6711(22)00512-4"}], "notes": [], "created": "2022-12-19T10:39:26.922Z", "modified": "2023-10-16T15:10:56.300Z"}, {"entity": "publication", "iuid": "ed2e8e4e4607450599075cb68f775f98", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ed2e8e4e4607450599075cb68f775f98.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ed2e8e4e4607450599075cb68f775f98"}}, "title": "Molecular profiling of stem cell-derived retinal pigment epithelial cell differentiation established for clinical translation.", "authors": [{"family": "Petrus-Reurer", "given": "Sandra", "initials": "S"}, {"family": "Lederer", "given": "Alex R", "initials": "AR"}, {"family": "Baqu\u00e9-Vidal", "given": "Laura", "initials": "L"}, {"family": "Douagi", "given": "Iyadh", "initials": "I"}, {"family": "Pannagel", "given": "Belinda", "initials": "B"}, {"family": "Khven", "given": "Irina", "initials": "I"}, {"family": "Aronsson", "given": "Monica", "initials": "M"}, {"family": "Bartuma", "given": "Hammurabi", "initials": "H"}, {"family": "Wagner", "given": "Magdalena", "initials": "M"}, {"family": "Wrona", "given": "Andreas", "initials": "A"}, {"family": "Efstathopoulos", "given": "Paschalis", "initials": "P"}, {"family": "Jaberi", "given": "Elham", "initials": "E"}, {"family": "Willenbrock", "given": "Hanni", "initials": "H"}, {"family": "Shimizu", "given": "Yutaka", "initials": "Y"}, {"family": "Villaescusa", "given": "J Carlos", "initials": "JC"}, {"family": "Andr\u00e9", "given": "Helder", "initials": "H"}, {"family": "Sundstr\u04e7m", "given": "Erik", "initials": "E"}, {"family": "Bhaduri", "given": "Aparna", "initials": "A"}, {"family": "Kriegstein", "given": "Arnold", "initials": "A"}, {"family": "Kvanta", "given": "Anders", "initials": "A"}, {"family": "La Manno", "given": "Gioele", "initials": "G"}, {"family": "Lanner", "given": "Fredrik", "initials": "F"}], "type": "journal article", "published": "2022-06-14", "journal": {"title": "Stem Cell Reports", "issn": "2213-6711", "issn-l": "2213-6711", "volume": "17", "issue": "6", "pages": "1458-1475"}, "abstract": "Human embryonic stem cell-derived retinal pigment epithelial cells (hESC-RPE) are a promising cell source to treat age-related macular degeneration (AMD). Despite several ongoing clinical studies, a detailed mapping of transient cellular states during in vitro differentiation has not been performed. Here, we conduct single-cell transcriptomic profiling of an hESC-RPE differentiation protocol that has been developed for clinical use. Differentiation progressed through a culture diversification recapitulating early embryonic development, whereby cells rapidly acquired a rostral embryo patterning signature before converging toward the RPE lineage. At intermediate steps, we identified and examined the potency of an NCAM1+ retinal progenitor population and showed the ability of the protocol to suppress non-RPE fates. We demonstrated that the method produces a pure RPE pool capable of maturing further after subretinal transplantation in a large-eyed animal model. Our evaluation of hESC-RPE differentiation supports the development of safe and efficient pluripotent stem cell-based therapies for AMD.", "doi": "10.1016/j.stemcr.2022.05.005", "pmid": "35705015", "labels": {"National Genomics Infrastructure": "Service", "NGI Short read": "Service", "Eukaryotic Single Cell Genomics (ESCG)": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Single cell": "Service", "NGI Stockholm (Genomics Production)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9214069"}, {"db": "pii", "key": "S2213-6711(22)00257-0"}], "notes": [], "created": "2022-08-19T08:38:01.135Z", "modified": "2023-10-12T12:29:34.915Z"}, {"entity": "publication", "iuid": "5dad7c12343547f896bfd2a78f6ed0b3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5dad7c12343547f896bfd2a78f6ed0b3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5dad7c12343547f896bfd2a78f6ed0b3"}}, "title": "The SARS-CoV-2 receptor ACE2 is expressed in mouse pericytes but not endothelial cells: Implications for COVID-19 vascular research.", "authors": [{"family": "Muhl", "given": "Lars", "initials": "L"}, {"family": "He", "given": "Liqun", "initials": "L"}, {"family": "Sun", "given": "Ying", "initials": "Y"}, {"family": "Andaloussi M\u00e4e", "given": "Maarja", "initials": "M"}, {"family": "Pietil\u00e4", "given": "Riikka", "initials": "R"}, {"family": "Liu", "given": "Jianping", "initials": "J"}, {"family": "Genov\u00e9", "given": "Guillem", "initials": "G"}, {"family": "Zhang", "given": "Lei", "initials": "L"}, {"family": "Xie", "given": "Yuan", "initials": "Y"}, {"family": "Leptidis", "given": "Stefanos", "initials": "S"}, {"family": "Mocci", "given": "Giuseppe", "initials": "G"}, {"family": "Stritt", "given": "Simon", "initials": "S"}, {"family": "Osman", "given": "Ahmed", "initials": "A"}, {"family": "Anisimov", "given": "Andrey", "initials": "A"}, {"family": "Hemanthakumar", "given": "Karthik Amudhala", "initials": "KA"}, {"family": "R\u00e4s\u00e4nen", "given": "Markus", "initials": "M"}, {"family": "Hansson", "given": "Emil M", "initials": "EM"}, {"family": "Bj\u00f6rkegren", "given": "Johan", "initials": "J"}, {"family": "Vanlandewijck", "given": "Michael", "initials": "M"}, {"family": "Blomgren", "given": "Klas", "initials": "K"}, {"family": "M\u00e4kinen", "given": "Taija", "initials": "T"}, {"family": "Peng", "given": "Xiao-Rong", "initials": "XR"}, {"family": "Hu", "given": "Yizhou", "initials": "Y"}, {"family": "Ernfors", "given": "Patrik", "initials": "P"}, {"family": "Arnold", "given": "Thomas D", "initials": "TD"}, {"family": "Alitalo", "given": "Kari", "initials": "K"}, {"family": "Lendahl", "given": "Urban", "initials": "U"}, {"family": "Betsholtz", "given": "Christer", "initials": "C"}], "type": "journal article", "published": "2022-05-10", "journal": {"title": "Stem Cell Reports", "issn": "2213-6711", "volume": "17", "issue": "5", "pages": "1089-1104", "issn-l": "2213-6711"}, "abstract": "Humanized mouse models and mouse-adapted SARS-CoV-2 virus are increasingly used to study COVID-19 pathogenesis, so it is important to learn where the SARS-CoV-2 receptor ACE2 is expressed. Here we mapped ACE2 expression during mouse postnatal development and in adulthood. Pericytes in the CNS, heart, and pancreas express ACE2 strongly, as do perineurial and adrenal fibroblasts, whereas endothelial cells do not at any location analyzed. In a number of other organs, pericytes do not express ACE2, including in the lung where ACE2 instead is expressed in bronchial epithelium and alveolar type II cells. The onset of ACE2 expression is organ specific: in bronchial epithelium already at birth, in brain pericytes before, and in heart pericytes after postnatal day 10.5. Establishing the vascular localization of ACE2 expression is central to correctly interpret data from modeling COVID-19 in the mouse and may shed light on the cause of vascular COVID-19 complications.", "doi": "10.1016/j.stemcr.2022.03.016", "pmid": "35452595", "labels": {"Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9022216"}, {"db": "pii", "key": "S2213-6711(22)00149-7"}], "notes": [], "created": "2023-11-27T21:45:20.067Z", "modified": "2024-01-16T13:48:36.559Z"}, {"entity": "publication", "iuid": "6733f592fb4a45bf9135c7dcc59e9c3d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6733f592fb4a45bf9135c7dcc59e9c3d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6733f592fb4a45bf9135c7dcc59e9c3d"}}, "title": "Generation of Retinal Pigment Epithelial Cells Derived from Human Embryonic Stem Cells Lacking Human Leukocyte Antigen Class I and II.", "authors": [{"family": "Petrus-Reurer", "given": "Sandra", "initials": "S"}, {"family": "Winblad", "given": "Nerges", "initials": "N"}, {"family": "Kumar", "given": "Pankaj", "initials": "P"}, {"family": "Gorchs", "given": "Laia", "initials": "L"}, {"family": "Chrobok", "given": "Michael", "initials": "M"}, {"family": "Wagner", "given": "Arnika Kathleen", "initials": "AK"}, {"family": "Bartuma", "given": "Hammurabi", "initials": "H"}, {"family": "Lardner", "given": "Emma", "initials": "E"}, {"family": "Aronsson", "given": "Monica", "initials": "M"}, {"family": "Plaza Reyes", "given": "\u00c1lvaro", "initials": "\u00c1"}, {"family": "Andr\u00e9", "given": "Helder", "initials": "H"}, {"family": "Alici", "given": "Evren", "initials": "E"}, {"family": "Kaipe", "given": "Helen", "initials": "H"}, {"family": "Kvanta", "given": "Anders", "initials": "A"}, {"family": "Lanner", "given": "Fredrik", "initials": "F"}], "type": "journal article", "published": "2020-04-14", "journal": {"title": "Stem Cell Reports", "issn": "2213-6711", "volume": "14", "issue": "4", "pages": "648-662", "issn-l": "2213-6711"}, "abstract": "Human embryonic stem cell-derived retinal pigment epithelial (hESC-RPE) cells could serve as a replacement therapy in advanced stages of age-related macular degeneration. However, allogenic hESC-RPE transplants trigger immune rejection, supporting a strategy to evade their immune recognition. We established single-knockout beta-2 microglobulin (SKO-B2M), class II major histocompatibility complex transactivator (SKO-CIITA) and double-knockout (DKO) hESC lines that were further differentiated into corresponding hESC-RPE lines lacking either surface human leukocyte antigen class I (HLA-I) or HLA-II, or both. Activation of CD4+ and CD8+ T-cells was markedly lower by hESC-RPE DKO cells, while natural killer cell cytotoxic response was not increased. After transplantation of SKO-B2M, SKO-CIITA, or DKO hESC-RPEs in a preclinical rabbit model, donor cell rejection was reduced and delayed. In conclusion, we have developed cell lines that lack both HLA-I and -II antigens, which evoke reduced T-cell responses in vitro together with reduced rejection in a large-eyed animal model.", "doi": "10.1016/j.stemcr.2020.02.006", "pmid": "32197113", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "S2213-6711(20)30062-X"}, {"db": "pmc", "key": "PMC7160308"}], "notes": [], "created": "2020-07-08T13:05:34.265Z", "modified": "2024-01-16T13:48:42.627Z"}, {"entity": "publication", "iuid": "1798d24fb91f49cabfed216c26dca811", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1798d24fb91f49cabfed216c26dca811.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1798d24fb91f49cabfed216c26dca811"}}, "title": "Modeling Motor Neuron Resilience in ALS Using Stem Cells.", "authors": [{"family": "Allodi", "given": "Ilary", "initials": "I"}, {"family": "Nijssen", "given": "Jik", "initials": "J"}, {"family": "Benitez", "given": "Julio Aguila", "initials": "JA"}, {"family": "Schweingruber", "given": "Christoph", "initials": "C"}, {"family": "Fuchs", "given": "Andrea", "initials": "A"}, {"family": "Bonvicini", "given": "Gillian", "initials": "G"}, {"family": "Cao", "given": "Ming", "initials": "M"}, {"family": "Kiehn", "given": "Ole", "initials": "O"}, {"family": "Hedlund", "given": "Eva", "initials": "E"}], "type": "journal article", "published": "2019-06-11", "journal": {"volume": "12", "issn": "2213-6711", "issue": "6", "pages": "1329-1341", "title": "Stem Cell Reports", "issn-l": "2213-6711"}, "abstract": "Oculomotor neurons, which regulate eye movement, are resilient to degeneration in the lethal motor neuron disease amyotrophic lateral sclerosis (ALS). It would be highly advantageous if motor neuron resilience could be modeled in vitro. Toward this goal, we generated a high proportion of oculomotor neurons from mouse embryonic stem cells through temporal overexpression of PHOX2A in neuronal progenitors. We demonstrate, using electrophysiology, immunocytochemistry, and RNA sequencing, that in vitro-generated neurons are bona fide oculomotor neurons based on their cellular properties and similarity to their in vivo counterpart in rodent and man. We also show that in vitro-generated oculomotor neurons display a robust activation of survival-promoting Akt signaling and are more resilient to the ALS-like toxicity of kainic acid than spinal motor neurons. Thus, we can generate bona fide oculomotor neurons in vitro that display a resilience similar to that seen in vivo.", "doi": "10.1016/j.stemcr.2019.04.009", "pmid": "31080111", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service"}, "xrefs": [{"db": "pii", "key": "S2213-6711(19)30131-6"}, {"db": "pmc", "key": "PMC6565614"}], "notes": [], "created": "2020-01-08T16:47:16.912Z", "modified": "2020-01-21T13:56:16.293Z"}, {"entity": "publication", "iuid": "a60e7870d37e4fc7b2d4daa9b9f62a4d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a60e7870d37e4fc7b2d4daa9b9f62a4d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a60e7870d37e4fc7b2d4daa9b9f62a4d"}}, "title": "Adult Neural Progenitor Cells Transplanted into Spinal Cord Injury Differentiate into Oligodendrocytes, Enhance Myelination, and Contribute to Recovery.", "authors": [{"family": "Sankavaram", "given": "Sreenivasa Raghavan", "initials": "SR"}, {"family": "Hakim", "given": "Ramil", "initials": "R"}, {"family": "Covacu", "given": "Ruxandra", "initials": "R"}, {"family": "Frostell", "given": "Arvid", "initials": "A"}, {"family": "Neumann", "given": "Susanne", "initials": "S"}, {"family": "Svensson", "given": "Mikael", "initials": "M"}, {"family": "Brundin", "given": "Lou", "initials": "L"}], "type": "journal article", "published": "2019-05-14", "journal": {"volume": "12", "issn": "2213-6711", "issue": "5", "pages": "950-966", "title": "Stem Cell Reports", "issn-l": "2213-6711"}, "abstract": "Long-term survival and integration of neural progenitor cells (NPCs) transplanted following spinal cord injury (SCI) have been observed. However, questions concerning the differentiation choice, the mechanism of action, and the contribution of NPCs to functional recovery remains unanswered. Therefore, we investigated the differentiation of NPCs, global transcriptomal changes in transplanted NPCs, the effect of NPCs on neuroinflammation, and the causality between NPC transplantation and functional recovery. We found that NPCs transplanted following SCI differentiate mainly into oligodendrocytes and enhance myelination, upregulate genes related to synaptic signaling and mitochondrial activity, and downregulate genes related to cytokine production and immune system response. NPCs suppress the expression of pro-inflammatory cytokines/chemokines; moreover, NPC ablation confirm that NPCs were responsible for enhanced recovery in hindlimb locomotor function. Understanding the reaction of transplanted NPCs is important for exploiting their full potential. Existence of causality implies that NPCs are useful in the treatment of SCI.", "doi": "10.1016/j.stemcr.2019.03.013", "pmid": "31031190", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service"}, "xrefs": [{"db": "pii", "key": "S2213-6711(19)30098-0"}, {"db": "pmc", "key": "PMC6524946"}], "notes": [], "created": "2020-01-08T16:47:15.594Z", "modified": "2020-01-21T13:56:16.277Z"}, {"entity": "publication", "iuid": "ea3c5fb6a9354e7e9c03e02d99b380de", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ea3c5fb6a9354e7e9c03e02d99b380de.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ea3c5fb6a9354e7e9c03e02d99b380de"}}, "title": "SQSTM1/p62-Directed Metabolic Reprogramming Is Essential for Normal Neurodifferentiation.", "authors": [{"family": "Calvo-Garrido", "given": "Javier", "initials": "J"}, {"family": "Maffezzini", "given": "Camilla", "initials": "C"}, {"family": "Schober", "given": "Florian A", "initials": "FA"}, {"family": "Clemente", "given": "Paula", "initials": "P"}, {"family": "Uhlin", "given": "Elias", "initials": "E"}, {"family": "Kele", "given": "Malin", "initials": "M"}, {"family": "Stranneheim", "given": "Henrik", "initials": "H"}, {"family": "Lesko", "given": "Nicole", "initials": "N"}, {"family": "Bruhn", "given": "Helene", "initials": "H"}, {"family": "Svenningsson", "given": "Per", "initials": "P"}, {"family": "Falk", "given": "Anna", "initials": "A"}, {"family": "Wedell", "given": "Anna", "initials": "A"}, {"family": "Freyer", "given": "Christoph", "initials": "C"}, {"family": "Wredenberg", "given": "Anna", "initials": "A"}], "type": "journal article", "published": "2019-04-09", "journal": {"volume": "12", "issn": "2213-6711", "issue": "4", "pages": "696-711", "title": "Stem Cell Reports", "issn-l": "2213-6711"}, "abstract": "Neurodegenerative disorders are an increasingly common and irreversible burden on society, often affecting the aging population, but their etiology and disease mechanisms are poorly understood. Studying monogenic neurodegenerative diseases with known genetic cause provides an opportunity to understand cellular mechanisms also affected in more complex disorders. We recently reported that loss-of-function mutations in the autophagy adaptor protein SQSTM1/p62 lead to a slowly progressive neurodegenerative disease presenting in childhood. To further elucidate the neuronal involvement, we studied the cellular consequences of loss of p62 in a neuroepithelial stem cell (NESC) model and differentiated neurons derived from reprogrammed p62 patient cells or by CRISPR/Cas9-directed gene editing in NESCs. Transcriptomic and proteomic analyses suggest that p62 is essential for neuronal differentiation by controlling the metabolic shift from aerobic glycolysis to oxidative phosphorylation required for neuronal maturation. This shift is blocked by the failure to sufficiently downregulate lactate dehydrogenase expression due to the loss of p62, possibly through impaired Hif-1\u03b1 downregulation and increased sensitivity to oxidative stress. The findings imply an important role for p62 in neuronal energy metabolism and particularly in the regulation of the shift between glycolysis and oxidative phosphorylation required for normal neurodifferentiation.", "doi": "10.1016/j.stemcr.2019.01.023", "pmid": "30827875", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Clinical Genomics Stockholm": "Service", "Bioinformatics Support for Computational Resources": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "S2213-6711(19)30025-6"}, {"db": "pmc", "key": "PMC6449840"}], "notes": [], "created": "2019-11-25T15:59:40.691Z", "modified": "2024-01-16T13:48:44.488Z"}, {"entity": "publication", "iuid": "e09108a2bbf24401ac214f19b104dc1a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e09108a2bbf24401ac214f19b104dc1a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e09108a2bbf24401ac214f19b104dc1a"}}, "title": "BMP Sustains Embryonic Stem Cell Self-Renewal through Distinct Functions of Different Kr\u00fcppel-like Factors.", "authors": [{"family": "Morikawa", "given": "Masato", "initials": "M"}, {"family": "Koinuma", "given": "Daizo", "initials": "D"}, {"family": "Mizutani", "given": "Anna", "initials": "A"}, {"family": "Kawasaki", "given": "Natsumi", "initials": "N"}, {"family": "Holmborn", "given": "Katarina", "initials": "K"}, {"family": "Sundqvist", "given": "Anders", "initials": "A"}, {"family": "Tsutsumi", "given": "Shuichi", "initials": "S"}, {"family": "Watabe", "given": "Tetsuro", "initials": "T"}, {"family": "Aburatani", "given": "Hiroyuki", "initials": "H"}, {"family": "Heldin", "given": "Carl-Henrik", "initials": "CH"}, {"family": "Miyazono", "given": "Kohei", "initials": "K"}], "type": "journal article", "published": "2016-01-12", "journal": {"volume": "6", "issn": "2213-6711", "issue": "1", "pages": "64-73", "title": "Stem Cell Reports", "issn-l": "2213-6711"}, "abstract": "Bone morphogenetic protein (BMP) signaling exerts paradoxical roles in pluripotent stem cells (PSCs); it sustains self-renewal of mouse embryonic stem cells (ESCs), while it induces differentiation in other PSCs, including human ESCs. Here, we revisit the roles of BMP-4 using mouse ESCs (mESCs) in naive and primed states. SMAD1 and SMAD5, which transduce BMP signals, recognize enhancer regions together with KLF4 and KLF5 in naive mESCs. KLF4 physically interacts with SMAD1 and suppresses its activity. Consistently, a subpopulation of cells with active BMP-SMAD can be ablated without disturbing the naive state of the culture. Moreover, Smad1/5 double-knockout mESCs stay in the naive state, indicating that the BMP-SMAD pathway is dispensable for it. In contrast, the MEK5-ERK5 pathway mediates BMP-4-induced self-renewal of mESCs by inducing Klf2, a critical factor for the ground state pluripotency. Our study illustrates that BMP exerts its self-renewing effect through distinct functions of different Kr\u00fcppel-like factors.", "doi": "10.1016/j.stemcr.2015.12.004", "pmid": "26771354", "labels": {"Genome Engineering Zebrafish": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S2213-6711(15)00369-0"}, {"db": "pmc", "key": "PMC4719190"}], "notes": [], "created": "2017-05-08T07:59:53.541Z", "modified": "2017-09-06T11:49:55.040Z"}], "created": "2017-05-09T09:12:31.253Z", "modified": "2020-11-27T13:14:09.607Z"}