Abstract: The present invention relates to the field of stem cell biology, in particular the lineage specific differentiation of pluripotent or multipotent stem cells, which can include, but is not limited to, human embryonic stem cells (hESC) in addition to nonembryonic human induced pluripotent stem cells (hiPSC), somatic stem cells, stem cells from patients with a disease, or any other cell capable of lineage specific differentiation. Specifically described are methods to direct the lineage specific differentiation of hESC and/or hiPSC into floor plate midbrain progenitor cells and then further into large populations of midbrain fate FOXA2+LMX1A+TH+ dopamine (DA) neurons using novel culture conditions.

Abstract: The presently disclosed subject matter provides for in vitro methods of inducing differentiation of human stem cells into neural crest, cranial placode or non-neuro ectoderm precursors, and cells generated by such methods. The presently disclosed subject matter also provides for uses of such cells for treating neurodegenerative and pituitary disorders.

Abstract: Cranial placodes are embryonic structures essential for sensory and endocrine organ development. The efficient derivation of cranial placodes from human pluripotent stem cells is disclosed where the timed removal of the BMP inhibitor Noggin, a component of the dual-SMAD inhibition strategy of neural induction, triggers placode induction at the expense of CNS fates. Further fate specification at the pre-placode stage enables the selective generation of placode-derived trigeminal ganglia capable of in vivo engraftment, mature lens fibers and anterior pituitary hormone-producing cells that upon transplantation produce hormones including, but not limited to, human growth hormone and adrenocortiocotropic hormone in vivo. Alternatively, anterior pituitary hormone-producing cells are generated in cell culture systems in vitro.

Abstract: The present disclosure provides methods for generating cortical excitatory neurons, cortical excitatory neurons generated by such methods, and composition comprising such cells. The present disclosure also provides uses of the cortical excitatory neurons and composition comprising thereof for preventing and/or treating neurodegenerative disorders.

Abstract: Provided are cortical interneurons and other neuronal cells and in vitro methods for producing such cortical interneurons and other neuronal cells by the directed differentiation of stem cells and neuronal progenitor cells. The present disclosure relates to novel methods of in vitro differentiation of stem cells and neural progenitor cells to produce several type neuronal cells and their precursor cells, including cortical interneurons, hypothalamic neurons and pre-optic cholinergic neurons. The present disclosure describes the derivation of these cells via inhibiting SMAD and Wnt signaling pathways and activating SHH signaling pathway. The present disclosure relates to the novel discovery that the timing and duration of SHH activation can be harnessed to direct controlled differentiation of neural progenitor cells into either cortical interneurons, hypothalamic neurons or pre-optic cholinergic neurons.

Abstract: The presently disclosed subject matter provides for in vitro methods of inducing differentiation of human stem cells into cortical neurons, and cortical neurons generated by such methods. The presently disclosed subject matter also provides for uses of such cortical neurons for treating neurodegenerative CNS disorders.

Abstract: Disclosed herein are methods and compositions for identifying transcriptional and epigenetic age-related markers. Disclosed herein are also methods and compositions for reprogramming cell age by modulating transcriptional and epigenetic age-related markers identified herein. The identified transcriptional and epigenetic age-related markers can also be used for measuring cellular age in a cell or tissue.

Abstract: The present invention relates generally to the field of cell biology of stem cells, more specifically the directed differentiation of pluripotent or multipotent stem cells, including human embryonic stem cells (hESC), somatic stem cells, and induced human pluripotent stem cells (hiPSC) using novel culture conditions. Specifically, methods are provided for obtaining neural tissue, floor plate cells, and placode including induction of neural plate development in hESCs for obtaining midbrain dopamine (DA) neurons, motor neurons, and sensory neurons. Further, neural plate tissue obtained using methods of the present inventions are contemplated for use in co-cultures with other tissues as inducers for shifting differentiation pathways, i.e. patterning.

Abstract: Provided are cortical interneurons and other neuronal cells and in vitro methods for producing such cortical interneurons and other neuronal cells by the directed differentiation of stem cells and neuronal progenitor cells. The present disclosure relates to novel methods of in vitro differentiation of stem cells and neural progenitor cells to produce several type neuronal cells and their precursor cells, including cortical interneurons, hypothalamic neurons and pre-optic cholinergic neurons. The present disclose describes the derivation of these cells via inhibiting SMAD and Wnt signaling pathways and activating SHH signaling pathway. The present disclosure relates to the novel discovery that the timing and duration of SHH activation can be harnessed to direct controlled differentiation of neural progenitor cells into either cortical interneurons, hypothalamic neurons or pre-optic cholinergic neurons.

Abstract: The present disclosure provides methods for generating midbrain dopamine neurons and precursors thereof, midbrain dopamine neurons and precursors thereof generated by such methods and compositions comprising such cells, and uses thereof for preventing, modeling, and/or treating a neurological disorder.

Abstract: Cranial placodes are embryonic structures essential for sensory and endocrine organ development. The efficient derivation of cranial placodes from human pluripotent stem cells is disclosed where the timed removal of the BMP inhibitor Noggin, a component of the dual-SMAD inhibition strategy of neural induction, triggers placode induction at the expense of CNS fates. Further fate specification at the pre-placode stage enables the selective generation of placode-derived trigeminal ganglia capable of in vivo engraftment, mature lens fibers and anterior pituitary hormone-producing cells that upon transplantation produce hormones including, but not limited to, human growth hormone and adrenocortiocotropic hormone in vivo. Alternatively, anterior pituitary hormone-producing cells are generated in cell culture systems in vitro.

Abstract: The present invention relates generally to the field of cell biology of stem cells, more specifically the directed differentiation of pluripotent or multipotent stem cells, including human embryonic stem cells (hESC), somatic stem cells, and induced human pluripotent stem cells (hiPSC) using novel culture conditions. Specifically, methods are provided for obtaining neural tissue, floor plate cells, and placode including induction of neural plate development in hESCs for obtaining midbrain dopamine (DA) neurons, motor neurons, and sensory neurons. Further, neural plate tissue obtained using methods of the present inventions are contemplated for use in co-cultures with other tissues as inducers for shifting differentiation pathways, i.e. patterning.

Abstract: The presently disclosed subject matter provides for in vitro methods of inducing differentiation of stem cells (e.g., human stem cells) into proprioceptors, proprioceptors generated by such methods, and compositions comprising such proprioceptors. The presently disclosed subject matter also provides for uses of such proprioceptors for preventing and/or treating disorders of proprioceptor neurons and/or neurodegenerative disorders (e.g., Friedreich's Ataxia).

Abstract: The presently disclosed subject matter provides for in vitro methods of inducing differentiation of human stem cells into neural crest, cranial placode or non-neuro ectoderm precursors, and cells generated by such methods. The presently disclosed subject matter also provides for uses of such cells for treating neurodegenerative and pituitary disorders.

Abstract: The present invention relates to the field of stem cell biology, in particular the linage specific differentiation of pluripotent or multipotent stem cells, which can include, but is not limited to, human embryonic stem cells (hESC), human induced pluripotent stem cells (hiPSC), somatic stem cells, cancer stem cells, or any other cell capable of lineage specific differentiation. Specifically described are methods to direct the lineage specific differentiation of hESC and/or hiPSC to nociceptors (i.e. nociceptor cells) using novel culture conditions. The nociceptors made using the methods of the present invention are further contemplated for various uses including, but limited to, use in in vitro drug discovery assays, pain research, and as a therapeutic to reverse disease of, or damage to, the peripheral nervous system (PNS). Further, compositions and methods are provided for producing melanocytes from human pluripotent stem cells for use in disease modeling.

Abstract: The present disclosure provides methods for generating midbrain dopamine neurons (mDAs) and precursors thereof, mDAs and precursors thereof generated by such methods and compositions comprising such cells, and uses thereof for preventing and/or treating neurological disorders. The present disclosure further provides methods of isolating mDAs and precursors thereof from a cell population using novel surface markers.

Abstract: The presently disclosed subject matter provides for in vitro methods of inducing differentiation of human stem cells into neural crest, cranial placode or non-neuro ectoderm precursors, and cells generated by such methods. The presently disclosed subject matter also provides for uses of such cells for treating neurodegenerative and pituitary disorders.

Abstract: The present disclosure relates to pluripotent stem cell (e.g., human PSC) based multiplex methods and compositions for identifying genes associated with the pathogenesis of a disorder (e.g., human disorder) and the responsiveness to certain treatments to such disorder. The present disclosure also provides genetic markers for identifying clinically relevant subpopulations of autism patients.

Abstract: The present disclosure relates to methods for generating microglial cells derived from stem cells (e.g., human stem cells), microglial cells obtained from such methods and compositions comprising thereof, and uses of said microglial cells for disease modeling and for treating microglia related disorders.

Abstract: The presently disclosed subject matter provides for in vitro methods of inducing differentiation of human stem cells into midbrain dopamine neurons, and precursors thereof, and cells generated by such methods. The presently disclosed subject matter also provides for uses of such cells for treating neurodegenerative disorders.