Identification and Single-Cell Functional Characterization of an Endodermally Biased Pluripotent Substate in Human Embryonic Stem Cells.
Identification and Single-Cell Functional Characterization of an Endodermally Biased Pluripotent Substate in Human Embryonic Stem Cells.
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DOI：
10.1016/j.stemcr.2018.04.015
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发表时间：
2018-06-05
影响因子：
5.9
通讯作者：
Andrews PW
中科院分区：
文献类型：
--
作者：
Allison TF;Smith AJH;Anastassiadis K;Sloane-Stanley J;Biga V;Stavish D;Hackland J;Sabri S;Langerman J;Jones M;Plath K;Coca D;Barbaric I;Gokhale P;Andrews PW
人类胚胎干细胞（hESC）显示出基因表达的显著异质性，这意味着干细胞隔室内存在离散的亚状态。为了确定这些亚状态是否影响hESC的命运决定，我们使用GFP报告细胞系来研究推定的未分化细胞的组分的性质，所述组分由它们的内胚层转录因子GATA 6与hESC表面标志物SSEA 3的差异表达定义。通过单细胞克隆，我们证实了以GATA 6和SSEA 3表达为特征的亚状态包括能够长期自我更新的多能干细胞。当克隆干细胞集落由GATA6阳性和GATA6阴性细胞形成时，更多来自GATA6阳性细胞的集落比来自GATA6阴性细胞的类似集落含有自发分化的内胚层细胞。我们使用单细胞转录组学分析来表征这些离散的细胞状态，确定SOX 17在建立内胚层偏向的干细胞状态中的潜在作用。hESC的亚群可以共表达多能性相关和谱系特异性基因hESC共表达GATA 6能够长期自我更新单个表达GATA 6的hESC再生GATA 6阴性细胞表达GATA 6的hESC在其分化倾向上是偏向的人胚胎干细胞具有在成人内转变为任何细胞类型的能力。Peter Andrews和他的同事们已经证明，单个细胞之间的细微差异可以在功能上偏向所产生的细胞类型。因此，产生和纯化这些偏向的细胞可以改善医学相关细胞类型的衍生。
Human embryonic stem cells (hESCs) display substantial heterogeneity in gene expression, implying the existence of discrete substates within the stem cell compartment. To determine whether these substates impact fate decisions of hESCs we used a GFP reporter line to investigate the properties of fractions of putative undifferentiated cells defined by their differential expression of the endoderm transcription factor, GATA6, together with the hESC surface marker, SSEA3. By single-cell cloning, we confirmed that substates characterized by expression of GATA6 and SSEA3 include pluripotent stem cells capable of long-term self-renewal. When clonal stem cell colonies were formed from GATA6-positive and GATA6-negative cells, more of those derived from GATA6-positive cells contained spontaneously differentiated endoderm cells than similar colonies derived from the GATA6-negative cells. We characterized these discrete cellular states using single-cell transcriptomic analysis, identifying a potential role for SOX17 in the establishment of the endoderm-biased stem cell state. Subsets of hESCs can co-express pluripotency-associated and lineage-specific genes hESCs co-expressing GATA6 are capable of long-term self-renewal Single GATA6-expressing hESCs regenerate GATA6-negative cells GATA6-expressing hESCs are biased in their propensity for differentiation Human embryonic stem cells have the capacity to turn into any cell type within the adult. Peter Andrews and colleagues have shown that subtle differences between individual cells can functionally bias the resulting cell type that is produced. Generating and purifying these biased cells may therefore improve the derivation of medically relevant cell types.
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影响因子：
23.9
作者：
Hayashi K;de Sousa Lopes SMC;Tang F;Lao K;Surani MA
通讯作者：
Surani MA
影响因子：
11.8
作者：
Chazaud, Claire;Yamanaka, Yojiro;Rossant, Janet
通讯作者：
Rossant, Janet
影响因子：
5.2
作者：
McLean, Amanda B.;D'Amour, Kevin A.;Dalton, Stephen
通讯作者：
Dalton, Stephen
影响因子：
64.8
作者：
Chang, Hannah H.;Hemberg, Martin;Huang, Sui
通讯作者：
Huang, Sui
影响因子：
2.7
作者：
FENDERSON, BA;ANDREWS, PW;HAKOMORI, SI
通讯作者：
HAKOMORI, SI