更新于：2024-05-01

BHLHE22

basic helix-loop-helix family member e22

更新于：2024-05-01

基本信息

别名

basic helix-loop-helix family member e22、Beta3、BHLHB5

+ [6]

简介

Inhibits DNA binding of TCF3/E47 homodimers and TCF3 (E47)/NEUROD1 heterodimers and acts as a strong repressor of Neurod1 and Myod-responsive genes, probably by heterodimerization with class a basic helix-loop-helix factors. Despite the presence of an intact basic domain, does not bind to DNA (By similarity). In the brain, may function as an area-specific transcription factor that regulates the postmitotic acquisition of area identities and elucidate the genetic hierarchy between progenitors and postmitotic neurons driving neocortical arealization. May be required for the survival of a specific population of inhibitory neurons in the superficial laminae of the spinal cord dorsal horn that may regulate pruritis. Seems to play a crucial role in the retinogenesis, in the specification of amacrine and bipolar subtypes. Forms with PRDM8 a transcriptional repressor complex controlling genes involved in neural development and neuronal differentiation.

关联

100 项与 BHLHE22 相关的临床结果

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100 项与 BHLHE22 相关的转化医学

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0 项与 BHLHE22 相关的专利（医药）

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419

项与 BHLHE22 相关的文献（医药）

2024-02-16·PLoS biology

Defining morphologically and genetically distinct GAGBergic/cholinergic amacrine cell subtypes in the vertebrate retina.

Article

作者: Yan Li ; Shuguang Yu ; Xinling Jia ; Xiaoying Qiu ; Jie He

In mammals, retinal direction selectivity originates from GABAergic/cholinergic amacrine cells (ACs) specifically expressing the sox2 gene. However, the cellular diversity of GABAergic/cholinergic ACs of other vertebrate species remains largely unexplored. Here, we identified 2 morphologically and genetically distinct GABAergic/cholinergic AC types in zebrafish, a previously undescribed bhlhe22+ type and a mammalian counterpart sox2+ type. Notably, while sole sox2 disruption removed sox2+ type, the codisruption of bhlhe22 and bhlhe23 was required to remove bhlhe22+ type. Also, both types significantly differed in dendritic arbors, lamination, and soma position. Furthermore, in vivo two-photon calcium imaging and the behavior assay suggested the direction selectivity of both AC types. Nevertheless, the 2 types showed preferential responses to moving bars of different sizes. Thus, our findings provide new cellular diversity and functional characteristics of GABAergic/cholinergic ACs in the vertebrate retina.

2023-12-29·bioRxiv : the preprint server for biology

Molecular identification of wide-field amacrine cells in mouse retina that encode stimulus orientation.

作者: Silvia J Park ; Wanyu Lei ; John Pisano ; Andrea Orpia ; Jacqueline Minehart ; Joseph Pottackal ; Christin Hanke-Gogokhia ; Thomas E Zapadka ; Cheryl Clarkson-Paredes ; Anastas Popratiloff ; Sarah E Ross ; Joshua H Singer ; Jonathan B Demb

Visual information processing is sculpted by a diverse group of inhibitory interneurons in the retina called amacrine cells. Yet, for most of the >60 amacrine cell types, molecular identities and specialized functional attributes remain elusive. Here, we developed an intersectional genetic strategy to target a group of wide-field amacrine cells (WACs) in mouse retina that co-express the transcription factor Bhlhe22 and the Kappa Opioid Receptor (KOR; B/K WACs). B/K WACs feature straight, unbranched dendrites spanning over 0.5 mm (∼15° visual angle) and produce non-spiking responses to either light increments or decrements. Two-photon dendritic population imaging reveals Ca ²⁺ signals tuned to the physical orientations of B/K WAC dendrites, signifying a robust structure-function alignment. B/K WACs establish divergent connections with multiple retinal neurons, including unexpected connections with non-orientation-tuned ganglion cells and bipolar cells. Our work sets the stage for future comprehensive investigations of the most enigmatic group of retinal neurons: WACs.

2023-08-03·Ecotoxicology and environmental safety

Root system architecture and genomic plasticity to salinity provide insights into salt-tolerant traits in tall fescue.

Article

作者: Shugao Fan ; Erick Amombo ; Yanling Yin ; Gunagyang Wang ; Sheila Avoga ; Nan Wu ; Yating Li

Salinity is detrimental to soil health, plant growth, and crop productivity. Understanding salt tolerance mechanisms offers the potential to introduce superior crops, especially in coastal regions. Root system architecture (RSA) plasticity is vital for plant salt stress adaptation. Tall fescue is a promising forage grass in saline regions with scarce RSA studies. Here, we used the computer-integrated and -automated programs EZ-Rhizo II and ROOT-Vis II to analyze and identify natural RSA variations and adaptability to high salt stress at physiological and genetic levels in 17 global tall fescue accessions. Total root length rather than the number of lateral roots contribute more to water uptake and could be used to separate salt-tolerant (LS-11) and -sensitive accessions (PI531230). Comparative evaluation of LS-11 and PI531230 demonstrated that the lateral root length rather than the main root contributed more towards the total root length in LS-11. Also, high water uptake was associated with a larger lateral root vector and position while low water intake was associated with an insignificant correlation between root length, vector, and position. To examine candidate gene expression, we performed transcriptome and transcription analyses using high-throughput RNA sequencing and real-time quantitative PCR, respectively of the lateral and main roots. The main root displayed more differentially expressed genes than the lateral root. A Poisson comparison of LS-11 vs PI531230 demonstrated significant upregulation of PLASMA MEMBRANE AQUAPORIN 1 and AUXIN RESPONSE FACTOR 22 in both the main and lateral root, which are associated with transmembrane water transport and the auxin-activated signaling system, respectively. There is also an upregulation of BASIC HELIX-LOOP-HELIX 5 in the main root and a downregulation in the lateral root, which is ascribed to sodium ion transmembrane transport, as well as an upregulation of THE MEDIATOR COMPLEX 1 assigned to water transport in the lateral root and a downregulation in the main root. Gene-protein interaction analysis found that more genes interacting with aquaporins proteins were upregulated in the lateral root than in the main root. We inferred that deeper main roots with longer lateral roots emanating from the bottom of the main root were ideal for tall fescue water uptake and salt tolerance, rather than many shallow roots, and that, while both main lateral roots may play similar roles in salt sensing and water uptake, there are intrinsic genomic differences.

项与 BHLHE22 相关的新闻（医药）

2022-09-23

·生物谷

《自然》：华人科学家重磅成果，给成人神经再生提供了铁证！

该研究通过机器学习的方法，在单细胞分辨率下构建了首个人海马区imGCs在整个生命周期内的动态分子特征图谱，证明了成年后海马中仍然存在imGCs，具有发展为成熟的新颗粒细胞的能力。关于大脑神经元能否再生，一直是神经科学领域十分关注的问题。传统的观点认为大脑中的神经元在成年后难以再生，但也有研究表明在大脑的某些区域，如海马，即使在成年后，仍然具有一定的产生新神经元的功能[1]。目前的理论认为，在成年后海马的神经发生过程中，神经干细胞首先产生中间神经前体细胞和神经母细胞，然后分裂为未成熟的齿状回颗粒细胞（imGCs，接受大脑皮层信息输入的神经元），并逐渐变为新的成熟神经元[2]。然而由于海马未成熟神经元的标志物有限，且研究方法较为复杂，因此科学家们对其知之甚少。近期，来自宾夕法尼亚大学佩雷尔曼医学院的宋洪军和明国莉的研究团队，通过单核RNA测序（snRNA-seq）和基于机器学习的方法，对人一生中不同阶段的海马imGCs进行分析，构建了首个人全生命周期imGCs的分子特征，相关研究发表于《自然》杂志[3]。他们发现，在人的整个生命周期中，海马中均存在imGCs，婴儿期imGCs占到颗粒细胞总数量的9.4%，4岁以后则为3.1%~7.5%，并随着年龄的增长这一比例逐渐下降。与成熟颗粒细胞（mGCs）相比，imGCs的基因表达特征与神经发生及可塑性相关。同时，手术获得的人成年海马组织在体外培养后能够获得大量的imGCs，这些结果都支持成年大脑具有神经再生的功能。此外，研究人员还注意到，在阿尔茨海默病（AD）患者中，imGCs数量减少，且基因表达改变，表明了imGCs在AD中具有一定的研究价值。论文首页截图研究人员首先对4个婴儿（这一时期imGCs丰度较高[4]）的海马样本进行了snRNA-seq分析，并根据未成熟神经元标记DCX、颗粒细胞标记PROX1和CALB1（CALB1在某些imGCs表达，但在mGCs中表达更高）对细胞进行分类。他们发现传统的非监督聚类方法无法在snRNA-seq数据集中识别imGCs群体（在以PROX1为标志的颗粒细胞中，DCX+imGCs与其他细胞混合在一起，无法进一步分离）。通过统的非监督聚类方法无法识别imGCs 为了识别imGCs，研究人员尝试使用一种有监督机器学习方法来对细胞进行分类[5]。该方法通过对原型细胞的分子特征进行提取，进而对每个待分类细胞与原型细胞进行相似性分析，从而进行细胞分类。进行为了验证该方法的准确性，研究人员首先将其应用于不同年龄小鼠海马的单细胞测序（scRNA-seq）数据集（可准确区分神经母细胞、imGCs和mGCs）。紧接着，研究人员将小鼠海马数据集中颗粒细胞集群中的Dcx+Prox1+Calb1-imGCs细胞作为原型，同时还有主要的非神经元细胞类型的原型（星形胶质细胞、少突胶质细胞前体细胞和小胶质细胞），对模型进行训练。模型训练完成后，将其用于不同年龄阶段小鼠海马数据集的每个细胞进行分类，并将模型的分类与集群注释相比较，发现模型识别的未成熟神经元主要为imGCs和神经母细胞，且imGCs占到绝大多数。重要的是，该模型可区分imGCs与mGCs。因此，这种基于机器学习的方法可以有效地区分未成熟神经元和成熟神经元。紧接着，研究人员将该模型应用于婴儿海马数据集，以婴儿imGCs（Dcx+Prox1+Calb1-）和其他非神经元细胞（星形胶质细胞、少突胶质细胞前体细胞、成熟少突胶质细胞和小胶质细胞）为原型细胞进行分类，识别出样本中的imGCs。使用机器学习的方法识别人婴儿时期海马中imGCs 与mGCs相比，imGCs的基因表达特征与神经系统发育、神经发生和突触发生相关。此外，研究人员还发现，在婴儿齿状回标本中，93.8%的Dcx+Prox1+Calb1-imGCs表达STMN1（微管解聚蛋白），而91.4%的Stmn1+Prox1+细胞Dcx阳性（imGCs），20.7%的Stmn1+Prox1+细胞Calb1阳性（更大概率为mGCs），这提示了STMN1是imGCs潜在的生物标记。 STMN1是imGCs潜在的生物标记完善了方法学后，研究人员将此模型应用于不同生命阶段（出生前、儿童期、青春期、成年期和老年期）和区域的人脑样本。研究结果显示，在出生前，人海马区和前额叶皮质都含有丰富的未成熟神经元，其中大部分为imGCs。在出生后，在所有年龄段的每个海马区标本中，也都发现了与人类imGCs原型细胞高度相似的细胞。每个年龄组颗粒细胞中imGCs的平均百分比为：产前51.8%，婴儿期9.4%，4岁及以后的3.1-7.5%，并呈逐年下降趋势。不同生命阶段imGCs丰度为了找到不同生命阶段的人imGCs的共同分子特征，研究人员将imGCs与mGCs进行了比较，发现所有生命阶段的imGCs的基因表达与神经系统发育（如NEUROD1和BHLHE22）、离子转运（如FXYD7和KCNQ5）和神经元投射发育（如SEMA6D和NR2F1）更相关。与mGCs相比，imGCs的基因表达与神经再生与发育相关同时，研究人员还发现，imGCs的基因表达存在一定的时间规律，即随着人类发育而产生一定差异，包括谷氨酸受体信号通路的持续上调和神经元迁移和突触投射相关基因的下调。 imGCs的基因表达随年龄增长而发生变化此外，研究人员还探索了imGCs在不同大脑疾病中的潜在作用，对AD、自闭症谱系疾病、癫痫、抑郁症和精神分裂症疾病风险基因进行了富集分析，发现这些基因在特定年龄的imGCs中的选择性表达，且表达时间与这些疾病发病关键时期相吻合，如AD患者的风险基因在老年时期的imGCs表达更高，自闭症谱系疾病的风险基因在早期发育阶段的imGCs表达更高。多种疾病的风险基因在疾病发病关键时期相吻合而在AD患者样本中，海马中imGCs占颗粒细胞的比例远低于正常对照组，且与突触可塑性和信号转导相关的基因表达显著下调。细胞-细胞相互作用分析显示，AD患者的imGC与星形胶质细胞、少突胶质细胞前体细胞、GABA能中间神经元等的相互作用显著减少。这些结果都表明imGCs在AD中很可能起到一定的作用，具有潜在的研究价值。 AD患者海马中imGCs数量减少且功能失调最后，为了验证成年后海马产生新神经元的能力，研究人员对年龄从2-61岁的10个癫痫患者的海马样本进行体外培养，其中有8个在体外培养1-2周后可观察到EDU+Prox1+Calb1-新生颗粒细胞，且超过80%的细胞DCX或STMN1阳性。这些结果表明了成年海马后齿状回中仍可产生新的颗粒细胞。总的来说，该研究通过机器学习的方法，在单细胞分辨率下构建了首个人海马区imGCs在整个生命周期内的动态分子特征图谱，证明了成年后海马中仍然存在imGCs，具有发展为成熟的新颗粒细胞的能力。同时，研究人员还发现人不同生命阶段的imGCs存在差异表达的基因，且一些与疾病相关的风险基因可在特定阶段在imGCs中选择性表达，具有作为干预靶点的潜力。