Abstract: Described herein is a method for producing a chimeric non-human animal expressing a human a MYF5, MYOD, MRF4 gene or a combination thereof gene comprising: a) generating an MYF5, MYOD, MRF4 or combination thereof null non-human animal cell, wherein both copies of the non-human MYF5, MYOD, MRF4 gene or combination thereof carry a mutation that prevents production of functional MYF5, MYOD, MRF4 protein or combination thereof in said non-human animal; b) creating a MYF5, MYOD, MRF4 or combination thereof null non-human blastocyst by somatic cell nuclear transfer comprising fusing a nucleus from said MYF5, MYOD, MRF4 or combination thereof null non-human animal cell of a) into an enucleated non-human oocyte and activating said oocyte to divide so as to form an MYF5, MYOD, MRF4 or combination thereof null non-human blastocyst; c) introducing human stem cells into the MYF5, MYOD, MRF4 or combination null non-human blastocyst of b); and d) implanting said blastocyst from c) into a pseudopregnant surrogate non-human

Abstract: Provided herein are method to increase the efficiency of interspecies chimera generation.

Abstract: Described herein is a method for producing a chimeric non-human animal expressing a human ETV2 gene comprising: a) generating an ETV2 null non-human animal cell, wherein both copies of the non-human ETV2 gene carry a mutation that prevents production of functional ETV2 protein in said non-human animal; b) creating an ETV2 null non-human blastocyst by somatic cell nuclear transfer comprising fusing a nucleus from said ETV2 null non-human animal cell of a) into an enucleated non-human oocyte and activating said oocyte to divide so as to form an ETV2 null non-human blastocyst; c) introducing human stem cells into the ETV2 null non-human blastocyst of b); and d) implanting said blastocyst from c) into a pseudopregnant surrogate non-human animal to generate a chimeric non-human animal expressing human ETV2.

Abstract: A method is provided to enhance repair or regeneration of a mammalian cardiovascular system to include heart and/or vasculature comprising: administering to a mammal in need thereof a composition comprising an effective amount of an agent that elevates levels of Smo, Ptc1, Shh, Ihh, Dhh, Gli1, Gli2, or Mycn.

Abstract: Described herein is a method for producing a chimeric non-human animal expressing a human ETV2 gene comprising: a) generating an ETV2 null non-human animal cell, wherein both copies of the non-human ETV2 gene carry a mutation that prevents production of functional ETV2 protein in said non-human animal; b) creating an ETV2 null non-human blastocyst by somatic cell nuclear transfer comprising fusing a nucleus from said ETV2 null non-human animal cell of a) into an enucleated non-human oocyte and activating said oocyte to divide so as to form an ETV2 null non-human blastocyst; c) introducing human stem cells into the ETV2 null non-human blastocyst of b); and d) implanting said blastocyst from c) into a pseudopregnant surrogate non-human animal to generate a chimeric non-human animal expressing human ETV2.

Abstract: Developmental, stem cell and cancer biologists are interested in the molecular definition of cellular differentiation. Although single-cell RNA sequencing represents a transformational advance for global gene analyses, novel obstacles have emerged, including the computational management of dropout events, the reconstruction of biological pathways and the isolation of target cell populations. Provided herein is an algorithm named dpath that applies the concept of metagene entropy and allows the ranking of cells based on their differentiation potential. Also provided herein are self-organizing map (SOM) and random walk with restart (RWR) algorithms to separate the progenitors from the differentiated cells and reconstruct the lineage hierarchies in an unbiased manner. These algorithms were tested using single cells from Etv2-EYFP transgenic mouse embryos and reveal specific molecular pathways that direct differentiation programs involving the haemato-endothelial lineages.

Abstract: Described herein is a method for producing a chimeric non-human animal expressing a human NKX2-5, HANDII, TBX5 gene or a combination thereof gene comprising: a) generating a NKX2-5, HANDII, TBX5 or combination thereof null non-human animal cell, wherein both copies of the non-human NKX2-5, HANDII, TBX5 gene or combination thereof carry a mutation that prevents production of functional NKX2-5, HANDII, TBX5 protein or combination thereof in said non-human animal; b) creating a NKX2-5, HANDII, TBX5 or combination thereof null non-human blastocyst by somatic cell nuclear transfer comprising fusing a nucleus from said NKX2-5, HANDII, TBX5 or combination thereof null non-human animal cell of a) into an enucleated non-human oocyte and activating said oocyte to divide so as to form an NKX2-5, HANDII, TBX5 or combination thereof null non-human blastocyst; c) introducing human stem cells into the NKX2-5, HANDII, TBX5 or combination null non-human blastocyst of b); and d) implanting said blastocyst from c) into a pseudo

Abstract: Described herein is a method for producing a chimeric non-human animal expressing a human a MYF5, MYOD, MRF4 gene or a combination thereof gene comprising: a) generating an MYF5, MYOD, MRF4 or combination thereof null non-human animal cell, wherein both copies of the non-human MYF5, MYOD, MRF4 gene or combination thereof carry a mutation that prevents production of functional MYF5, MYOD, MRF4 protein or combination thereof in said non-human animal; b) creating a MYF5, MYOD, MRF4 or combination thereof null non-human blastocyst by somatic cell nuclear transfer comprising fusing a nucleus from said MYF5, MYOD, MRF4 or combination thereof null non-human animal cell of a) into an enucleated non-human cocyte and activating said oocyte to divide so as to form an MYF5, MYOD, MRF4 or combination thereof null non-human blastocyst; c) introducing human stem cells into the MYF5, MYOD, MRF4 or combination null non-human blastocyst of b); and d) implanting said blastocyst from c) into a pseudopregnant surrogate non-human

Abstract: Described herein is a method for producing a chimeric non-human animal expressing a human NKX2-5, HANDII, TBX5 gene or a combination thereof gene comprising: a) generating a NKX2-5, HANDII, TBX5 or combination thereof null non-human animal cell, wherein both copies of the non-human NKX2-5, HANDII, TBX5 gene or combination thereof carry a mutation that prevents production of functional NKX2-5, HANDII, TBX5 protein or combination thereof in said non-human animal; b) creating a NKX2-5, HANDII, TBX5 or combination thereof null non-human blastocyst by somatic cell nuclear transfer comprising fusing a nucleus from said NKX2-5, HANDII, TBX5 or combination thereof null non-human animal cell of a) into an enucleated non-human oocyte and activating said oocyte to divide so as to form an NKX2-5, HANDII, TBX5 or combination thereof null non-human blastocyst; c) introducing human stem cells into the NKX2-5, HANDII, TBX5 or combination null non-human blastocyst of b); and d) implanting said blastocyst from c) into a pseudo

Abstract: Provided herein are method to increase the efficiency of interspecies chimera generation.

Abstract: Described herein is a method for producing a chimeric non-human animal expressing a human a MYF5, MYOD, MRF4 gene or a combination thereof gene comprising: a) generating an MYF5, MYOD, MRF4 or combination thereof null non-human animal cell, wherein both copies of the non-human MYF5, MYOD, MRF4 gene or combination thereof carry a mutation that prevents production of functional MYF5, MYOD, MRF4 protein or combination thereof in said non-human animal; b) creating a MYF5, MYOD, MRF4 or combination thereof null non-human blastocyst by somatic cell nuclear transfer comprising fusing a nucleus from said MYF5, MYOD, MRF4 or combination thereof null non-human animal cell of a) into an enucleated non-human oocyte and activating said oocyte to divide so as to form an MYF5, MYOD, MRF4 or combination thereof null non-human blastocyst; c) introducing human stem cells into the MYF5, MYOD, MRF4 or combination null non-human blastocyst of b); and d) implanting said blastocyst from c) into a pseudopregnant surrogate non-human

Abstract: Disclosed is a method to differentiate stern, progenitor or precursor cells comprising contacting said stem, progenitor or precursor cells with miR-130a, or an RNA having at least 95% identity thereto, so as to yield cells of endothelial lineage. Further disclosed are compositions comprising the endothelial lineage cells obtained and methods of using the compositions for treating diseases including cardiovascular diseases.

Abstract: A method is provided to enhance repair or regeneration of a mammalian cardiovascular system to include heart and/or vasculature comprising: administering to a mammal in need thereof a composition comprising an effective amount of an agent that elevates levels of Smo, Ptc1, Shh, Ihh, Dhh, Gli1, Gli2, or Mycn,

Abstract: Disclosed is a method to differentiate stern, progenitor or precursor cells comprising contacting said stem, progenitor or precursor cells with miR-130a, or an RNA having at least 95% identity thereto, so as to yield cells of endothelial lineage. Further disclosed are compositions comprising the endothelial lineage cells obtained and methods of using the compositions for treating diseases including cardiovascular diseases.

Abstract: Described herein is a method for producing a chimeric non-human animal expressing a human NKX2-5, HANDII, TBX5 gene or a combination thereof gene comprising: a) generating a NKX2-5, HANDII, TBX5 or combination thereof null non-human animal cell, wherein both copies of the non-human NKX2-5, HANDII, TBX5 gene or combination thereof carry a mutation that prevents production of functional NKX2-5, HANDII, TBX5 protein or combination thereof in said non-human animal; b) creating a NKX2-5, HANDII, TBX5 or combination thereof null non-human blastocyst by somatic cell nuclear transfer comprising fusing a nucleus from said NKX2-5, HANDII, TBX5 or combination thereof null non-human animal cell of a) into an enucleated non-human oocyte and activating said oocyte to divide so as to form an NKX2-5, HANDII, TBX5 or combination thereof null non-human blastocyst; c) introducing human stem cells into the NKX2-5, HANDII, TBX5 or combination null non-human blastocyst of b); and d) implanting said blastocyst from c) into a pseudo

Abstract: Described herein is a method for producing a chimeric non-human animal expressing a human a MYF5, MYOD, MRF4 gene or a combination thereof gene comprising: a) generating an MYF5, MYOD, MRF4 or combination thereof null non-human animal cell, wherein both copies of the non-human MYF5, MYOD, MRF4 gene or combination thereof carry a mutation that prevents production of functional MYF5, MYOD, MRF4 protein or combination thereof in said non-human animal; b) creating a MYF5, MYOD, MRF4 or combination thereof null non-human blastocyst by somatic cell nuclear transfer comprising fusing a nucleus from said MYF5, MYOD, MRF4 or combination thereof null non-human animal cell of a) into an enucleated non-human oocyte and activating said oocyte to divide so as to form an MYF5, MYOD, MRF4 or combination thereof null non-human blastocyst; c) introducing human stem cells into the MYF5, MYOD, MRF4 or combination null non-human blastocyst of b); and d) implanting said blastocyst from c) into a pseudopregnant surrogate non-human

Abstract: Described herein is a method for producing a chimeric non-human animal expressing a human ETV2 gene comprising: a) generating an ETV2 null non-human animal cell, wherein both copies of the non-human ETV2 gene carry a mutation that prevents production of functional ETV2 protein in said non-human animal; b) creating an ETV2 null non-human blastocyst by somatic cell nuclear transfer comprising fusing a nucleus from said ETV2 null non-human animal cell of a) into an enucleated non-human oocyte and activating said oocyte to divide so as to form an ETV2 null non-human blastocyst; c) introducing human stem cells into the ETV2 null non-human blastocyst of b); and d) implanting said blastocyst from c) into a pseudopregnant surrogate non-human animal to generate a chimeric non-human animal expressing human ETV2.

Abstract: Developmental, stem cell and cancer biologists are interested in the molecular definition of cellular differentiation. Although single-cell RNA sequencing represents a transformational advance for global gene analyses, novel obstacles have emerged, including the computational management of dropout events, the reconstruction of biological pathways and the isolation of target cell populations. Provided herein is an algorithm named dpath that applies the concept of metagene entropy and allows the ranking of cells based on their differentiation potential. Also provided herein are self-organizing map (SOM) and random walk with restart (RWR) algorithms to separate the progenitors from the differentiated cells and reconstruct the lineage hierarchies in an unbiased manner. These algorithms were tested using single cells from Etv2-EYFP transgenic mouse embryos and reveal specific molecular pathways that direct differentiation programs involving the haemato-endothelial lineages.