Assoc.Prof. Parinya Noisa

Year	Title	Journal
2015	Combined negative effect of donor age and time in culture on the reprogramming efficiency into induced pluripotent stem cells Trokovic R., Weltner J., Noisa P., Raivio T., Otonkoski T.	Stem Cell Research
Abstract: Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSC) by the forced expression of the transcription factors OCT4, SOX2, KLF4 and c-MYC. Pluripotent reprogramming appears as a slow and inefficient process because of genetic and epigenetic barriers of somatic cells. In this report, we have extended previous observations concerning donor age and passage number of human fibroblasts as critical determinants of the efficiency of iPSC induction. Human fibroblasts from 11 different donors of variable age were reprogrammed by ectopic expression of reprogramming factors. Although all fibroblasts gave rise to iPSC colonies, the reprogramming efficiency correlated negatively and declined rapidly with increasing donor age. In addition, the late passage fibroblasts gave less reprogrammed colonies than the early passage cell counterparts, a finding associated with the cellular senescence-induced upregulation of p21. Knockdown of p21 restored iPSC generation even in long-term passaged fibroblasts of an old donor, highlighting the central role of the p53/p21 pathway in cellular senescence induced by both donor age and culture time. © 2015 Published by Elsevier B.V. Keyword: Scopus Link: https://www.scopus.com/inward/record.uri?eid=2-s2.0-84939464377&doi=10.1016%2fj.scr.2015.06.001&partnerID=40&md5=e68575f0ae6df7d90e56da5c075c942a DOI: 10.1016/j.scr.2015.06.001
2015	Neural progenitor cells derived from human embryonic stem cells as an origin of dopaminergic neurons Noisa P., Raivio T., Cui W.	Stem Cells International
Abstract: Human embryonic stem cells (hESCs) are able to proliferate in vitro indefnitely without losing their ability to differentiate into multiple cell types upon exposure to appropriate signals. Particularly, the ability of hESCs to differentiate into neuronal subtypes is fundamental to develop cell-based therapies for several neurodegenerative disorders, such as Alzheimer's disease, Huntington's disease, and Parkinson's disease. In this study, we differentiated hESCs to dopaminergic neurons via an intermediate stage, neural progenitor cells (NPCs). hESCs were induced to neural progenitor cells by Dorsomorphin, a small molecule that inhibits BMP signalling. The resulting neural progenitor cells exhibited neural bipolarity with high expression of neural progenitor genes and possessed multipotential differentiation ability. CBF1 and bFGF responsiveness of these hES-NP cells suggested their similarity to embryonic neural progenitor cells. A substantial number of dopaminergic neurons were derived from hES-NP cells upon supplementation of FGF8 and SHH, key dopaminergic neuron inducers. Importantly, multiple markers of midbrain neurons were detected, including NURR1, PITX3, and EN1, suggesting that hESC-derived dopaminergic neurons attained the midbrain identity. Altogether, this work underscored the generation of neural progenitor cells that retain the properties of embryonic neural progenitor cells. Tese cells will serve as an unlimited source for the derivation of dopaminergic neurons, which might be applicable for treating patients with Parkinson's disease. Copyright © 2015 Parinya Noisa et al. Keyword: Scopus Link: https://www.scopus.com/inward/record.uri?eid=2-s2.0-84929346590&doi=10.1155%2f2015%2f647437&partnerID=40&md5=3e09456d9d0bdfd238f124dabc0303c3 DOI: 10.1155/2015/647437
2014	Neural crest cells: From developmental biology to clinical interventions Noisa P., Raivio T.	Birth Defects Research Part C - Embryo Today: Reviews
Abstract: Neural crest cells are multipotent cells, which are specified in embryonic ectoderm in the border of neural plate and epiderm during early development by interconnection of extrinsic stimuli and intrinsic factors. Neural crest cells are capable of differentiating into various somatic cell types, including melanocytes, craniofacial cartilage and bone, smooth muscle, and peripheral nervous cells, which supports their promise for cell therapy. In this work, we provide a comprehensive review of wide aspects of neural crest cells from their developmental biology to applicability in medical research. We provide a simplified model of neural crest cell development and highlight the key external stimuli and intrinsic regulators that determine the neural crest cell fate. Defects of neural crest cell development leading to several human disorders are also mentioned, with the emphasis of using human induced pluripotent stem cells to model neurocristopathic syndromes. © 2014 Wiley Periodicals, Inc. Keyword: Human pluripotent stem cells; Neural crest cells; Neurocristopathies Scopus Link: https://www.scopus.com/inward/record.uri?eid=2-s2.0-84908501098&doi=10.1002%2fbdrc.21074&partnerID=40&md5=f19ab67d14cc37bb06c01d3f900f3909 DOI: 10.1002/bdrc.21074
2014	Notch signaling regulates the differentiation of neural crest from human pluripotent stem cells Noisa P., Lund C., Kanduri K., Lund R., Lähdesmäki H., Lahesmaa R., Lundin K., Chokechuwattanalert H., Otonkoski T., Tuuri T., Raivio T.	Journal of Cell Science
Abstract: Neural crest cells are specified at the border between the neural plate and the epiderm. They are capable of differentiating into various somatic cell types, including craniofacial and peripheral nerve tissues. Notch signaling plays important roles during neurogenesis; however, its function during human neural crest development is poorly understood. Here, we generated selfrenewing premigratory neural-crest-like cells (pNCCs) from human pluripotent stem cells (hPSCs) and investigated the roles of Notch signaling during neural crest differentiation. pNCCs expressed various neural-crest-specifier genes, including SLUG (also known as SNAI2), SOX10 and TWIST1, and were able to differentiate into most neural crest derivatives. Blocking Notch signaling during the pNCC differentiation suppressed the expression of neural-crestspecifier genes. By contrast, ectopic expression of activated Notch1 intracellular domain (NICD1) augmented the expression of neuralcrest-specifier genes, and NICD1 was found to bind to their promoter regions. Notch activity was also required for the maintenance of the premigratory neural crest state, and the suppression of Notch signaling led to the generation of neuralcrest-derived neurons. Taken together, we provide a protocol for the generation of pNCCs and show that Notch signaling regulates the formation, migration and differentiation of neural crest from hPSCs. © 2014. Published by The Company of Biologists Ltd. Keyword: Human embryonic stem cells; Human induced pluripotent stem cells; Neural crest; Notch signaling Scopus Link: https://www.scopus.com/inward/record.uri?eid=2-s2.0-84899763836&doi=10.1242%2fjcs.145755&partnerID=40&md5=dc07ab02dd347d627ad8ff9349ec9167 DOI: 10.1242/jcs.145755
2013	Biomedical and clinical promises of human pluripotent stem cells for neurological disorders Jongkamonwiwat N., Noisa P.	BioMed Research International
Abstract: Neurological disorders are characterized by the chronic and progressive loss of neuronal structures and functions. There is a variability of the onsets and causes of clinical manifestations. Cell therapy has brought a new concept to overcome brain diseases, but the advancement of this therapy is limited by the demands of specialized neurons. Human pluripotent stem cells (hPSCs) have been promised as a renewable resource for generating human neurons for both laboratory and clinical purposes. By the modulations of appropriate signalling pathways, desired neuron subtypes can be obtained, and induced pluripotent stem cells (iPSCs) provide genetically matched neurons for treating patients. These hPSC-derived neurons can also be used for disease modeling and drug screening. Since the most urgent problem today in transplantation is the lack of suitable donor organs and tissues, the derivation of neural progenitor cells from hPSCs has opened a new avenue for regenerative medicine. In this review, we summarize the recent reports that show how to generate neural derivatives from hPSCs, and discuss the current evidence of using these cells in animal studies. We also highlight the possibilities and concerns of translating these hPSC-derived neurons for biomedical and clinical uses in order to fight against neurological disorders. © 2013 Nopporn Jongkamonwiwat and Parinya Noisa. Keyword: Scopus Link: https://www.scopus.com/inward/record.uri?eid=2-s2.0-84885573576&doi=10.1155%2f2013%2f656531&partnerID=40&md5=bdcebbec73f5bff59e31e9a34050d081 DOI: 10.1155/2013/656531
2013	PROKR2 mutations in autosomal recessive Kallmann syndrome Tommiska J., Toppari J., Vaaralahti K., Känsäkoski J., Laitinen E.-M., Noisa P., Kinnala A., Niinikoski H., Raivio T.	Fertility and Sterility
Abstract: Objective: To investigate the inheritance pattern of two missense PROKR2 changes within a single family. Design: This is a descriptive study. Setting: Tertiary referral center. Patient(s): The proband and his brother, both with congenital hypogonadotropic hypogonadism and anosmia (Kallmann syndrome). Intervention(s): Clinical and biochemical evaluation of Kallmann syndrome. Sequence analysis of the coding exons and exon-intron boundaries of KAL1, FGFR1, FGF8, PROK2, and PROKR2 from polymerase chain reaction (PCR)-amplified genomic DNA. Recombinant human FSH treatment of the proband. Main Outcome Measure(s): Phenotypic and genotypic features, and inhibin B response to recombinant human FSH. Result(s): The proband and his brother were homozygous for two variants in PROKR2; a novel mutation c.701G>A (p.G234D), and a polymorphism c.802C>T (p.R268C). Recombinant human FSH therapy of the proband increased serum inhibin B from <16 to 136 ng/L. The heterozygous parents were fertile and had six children. Conclusion(s): These findings are consistent with recessive mode of inheritance. PROKR2 signaling does not directly affect Sertoli cell function. ©2013 by American Society for Reproductive Medicine. Keyword: biallelic mutations; hypogonadotropic hypogonadism; PROKR2; recessive inheritance Scopus Link: https://www.scopus.com/inward/record.uri?eid=2-s2.0-84875222270&doi=10.1016%2fj.fertnstert.2012.11.003&partnerID=40&md5=ddf3e113db700090896e322536239854 DOI: 10.1016/j.fertnstert.2012.11.003
2012	Identification and Characterisation of the Early Differentiating Cells in Neural Differentiation of Human Embryonic Stem Cells Noisa P., Ramasamy T.S., Lamont F.R., Yu J.S.L., Sheldon M.J., Russell A., Jin X., Cui W.	PLoS ONE
Abstract: One of the challenges in studying early differentiation of human embryonic stem cells (hESCs) is being able to discriminate the initial differentiated cells from the original pluripotent stem cells and their committed progenies. It remains unclear how a pluripotent stem cell becomes a lineage-specific cell type during early development, and how, or if, pluripotent genes, such as Oct4 and Sox2, play a role in this transition. Here, by studying the dynamic changes in the expression of embryonic surface antigens, we identified the sequential loss of Tra-1-81 and SSEA4 during hESC neural differentiation and isolated a transient Tra-1-81(-)/SSEA4(+) (TR-/S4+) cell population in the early stage of neural differentiation. These cells are distinct from both undifferentiated hESCs and their committed neural progenitor cells (NPCs) in their gene expression profiles and response to extracellular signalling; they co-express both the pluripotent gene Oct4 and the neural marker Pax6. Furthermore, these TR-/S4+ cells are able to produce cells of both neural and non-neural lineages, depending on their environmental cues. Our results demonstrate that expression of the pluripotent factor Oct4 is progressively downregulated and is accompanied by the gradual upregulation of neural genes, whereas the pluripotent factor Sox2 is consistently expressed at high levels, indicating that these pluripotent factors may play different roles in the regulation of neural differentiation. The identification of TR-S4+ cells provides a cell model for further elucidation of the molecular mechanisms underlying hESC neural differentiation. © 2012 Noisa et al. Keyword: Scopus Link: https://www.scopus.com/inward/record.uri?eid=2-s2.0-84870817505&doi=10.1371%2fjournal.pone.0037129&partnerID=40&md5=14a3831a5510ba95cee2e88728fedadc DOI: 10.1371/journal.pone.0037129
2012	DLK1 Promotes Neurogenesis of Human and Mouse Pluripotent Stem Cell-Derived Neural Progenitors Via Modulating Notch and BMP Signalling Surmacz B., Noisa P., Risner-Janiczek J.R., Hui K., Ungless M., Cui W., Li M.	Stem Cell Reviews and Reports
Abstract: A better understanding of the control of stem cell maintenance and differentiation fate choice is fundamental to effectively realising the potential of human pluripotent stem cells in disease modelling, drug screening and cell therapy. Dlk1 is a Notch related transmembrane protein that has been reportedly expressed in several neurogenic regions in the developing brain. In this study, we investigated the ability of Dlk1 in modulating the maintenance and differentiation of human and mouse ESC-derived neural progenitors. We found that DLK1, either employed as an extrinsic factor, or via transgene expression, consistently promoted the generation of neurons in both the mouse and human ESC-derived neural progenitors. DLK1 exerts this function by inducing cell cycle exit of the progenitors, as evidenced by an increase in the number of young neurons retaining BrdU labelling and cells expressing the cycling inhibitor P57Kip2. DLK1 antagonised the cell proliferation activity of Notch ligands Delta 1 and Jagged and inhibited Hes1-mediated Notch signaling as demonstrated by a luciferase reporter assay. Interestingly, we found that DLK1 promotes the neurogenic potential of human neural progenitor cells via suppression of Smad activation when they are challenged with BMP. Together, our data demonstrate for the first time a regulatory role for DLK1 in human and mouse neural progenitor differentiation and establish an interaction between DLK1 and Hes1-mediated Notch signaling in these cells. Furthermore, this study identifies DLK1 as a novel modulator of BMP/Smad signalling. © 2011 Springer Science+Business Media, LLC. Keyword: Differentiation; Embryonic stem cell (ESC); Neural progenitor; Notch signaling; Proliferation Scopus Link: https://www.scopus.com/inward/record.uri?eid=2-s2.0-84861682732&doi=10.1007%2fs12015-011-9298-7&partnerID=40&md5=36ba486771532e1c2f6b2ce856c3b455 DOI: 10.1007/s12015-011-9298-7
2011	Modeling neurological disorders by human induced pluripotent stem cells Kunkanjanawan T., Noisa P., Parnpai R.	Journal of Biomedicine and Biotechnology
Abstract: Studies of human brain development are critical as research on neurological disorders have been progressively advanced. However, understanding the process of neurogenesis through analysis of the early embryo is complicated and limited by a number of factors, including the complexity of the embryos, availability, and ethical constrains. The emerging of human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) has shed light of a new approach to study both early development and disease pathology. The cells behave as precursors of all embryonic lineages; thus, they allow tracing the history from the root to individual branches of the cell lineage tree. Systems for neural differentiation of hESCs and iPSCs have provided an experimental model that can be used to augment in vitro studies of in vivo brain development. Interestingly, iPSCs derived from patients, containing donor genetic background, have offered a breakthrough approach to study human genetics of neurodegenerative diseases. This paper summarizes the recent reports of the development of iPSCs from patients who suffer from neurological diseases and evaluates the feasibility of iPSCs as a disease model. The benefits and obstacles of iPSC technology are highlighted in order to raising the cautions of misinterpretation prior to further clinical translations. © 2011 Tanut Kunkanjanawan et al. Keyword: Scopus Link: https://www.scopus.com/inward/record.uri?eid=2-s2.0-84855546273&doi=10.1155%2f2011%2f350131&partnerID=40&md5=da2b90405e40c47e9cacd4147c2e1729 DOI: 10.1155/2011/350131
2011	Technical challenges in the derivation of human pluripotent cells Noisa P., Parnpai R.	Stem Cells International
Abstract: It has long been discovered that human pluripotent cells could be isolated from the blastocyst state of embryos and called human embryonic stem cells (ESCs). These cells can be adapted and propagated indefinitely in culture in an undifferentiated manner as well as differentiated into cell representing the three major germ layers: endoderm, mesoderm, and ectoderm. However, the derivation of human pluripotent cells from donated embryos is limited and restricted by ethical concerns. Therefore, various approaches have been explored and proved their success. Human pluripotent cells can also be derived experimentally by the nuclear reprogramming of somatic cells. These techniques include somatic cell nuclear transfer (SCNT), cell fusion and overexpression of pluripotent genes. In this paper, we discuss the technical challenges of these approaches for nuclear reprogramming, involving their advantages and limitations. We will also highlight the possible applications of these techniques in the study of stem cell biology. Copyright © 2011 Parinya Noisa and Rangsun Parnpai. Keyword: Scopus Link: https://www.scopus.com/inward/record.uri?eid=2-s2.0-80052720546&doi=10.4061%2f2011%2f907961&partnerID=40&md5=b6c8df7d86eabfa41fde88bf5620ceae DOI: 10.4061/2011/907961