Human Stem Cells/HSC & Development （人类干细胞和造血干细胞及其发育）

 

【Sperm (精子)+ Ovum (卵子)】 （Fertilization 受精）→ Zygote (受精卵，合子) → 4/8/16 cell stage (4/8/16细胞期)  →   Blastocyst (囊胚) (Trophoblast滋养层  Blastocoel胚囊腔  Inner cell mass 内细胞团)   →→→郑州大学一附院血液内科万鼎铭

Ⅰ：Gastrula(原肠胚期)（Ectoderm外胚层 Mesoderm中胚层Endoderm内胚层）→      Fetus(胎儿) [Somatic stem cell 成体干细胞（Self renewal自我更新）   →     Terminally differentiated cell type (终末分化的细胞类型) (Inducible expression of transcription factors转录因子的诱导表达：Oct-4, Sox2, c-Myc, Klf4 etc)]   →      Induced pluripotent stem cell (IPSC 诱导多能干细胞)

Ⅱ：Embryonic stem cells （ESC胚胎干细胞）（Self renewal自我更新）

 

【ESC（胚胎干细胞）Or IPSC（诱导多能干细胞）】(CD9，CD15，CD24，CD29，CD30，CD49f, CD133，CD324，CD338，CCR4，Frizzled-5, GCTM-2, Podocalyxin, SSEA-3, SSEA-4, TRA-1-60 Antigen, TRA-1-18 Atigen etc)  →→→

Ⅰ：Primitive streak (原条) →→

1. Mesodermal embryonic stem cell(中胚层胚胎干细胞)(CD31,CD34,CD325) → Immature mesoderm(未成熟中胚层) →→

①Paraxial mesoderm(轴旁中胚层) → Hemangioblast(成血管血液干细胞)（CD31,CD34,CD133,CD143,CD144,CD202b,CD309,CD324,EphB4,Podocalyxin）→  A.  Hematopoietic stem cell (造血干细胞) ( CD34, CD38^-, CD90, CD105, CD106, CD117, CD133, CD164, CD184, CD202b, CD338, FLK-1, Notch-1)    B.    Endothelial cells(内皮细胞) (CD31,CD34,CD62E,CD105,CD106) → Hematopoietic stem cell (造血干细胞)

② Lateral mesoderm(侧中胚层) (CD5, CD10, CD13, CD14, C15, CD29, CD31, CD44, CD49d, CD49f, CD54, CD71, CD72, CD73, CD90, CD105, CD106, STRO-1) → Mesenchymal stem cell (间充质干细胞)（CD44, CD45^-, CD73, CD90, CD105, CD166） → Cartilage软骨, Fibroblast成纤维细胞(Tendon腱 & Ligament韧带 &  Skin皮肤),Stromal cell基质细胞, Osteocyte骨细胞, Astrocyte星形胶质细胞, Adipocyte脂肪细胞, Myocyte肌细胞（Cardiac muscle, Smooth muscle, Skeletal muscle）

 

【Hematopoietic stem cell (HSC造血干细胞)】( CD34, CD38^-, CD90, CD105, CD106, CD117, CD133, CD164, CD184, CD202b, CD338, FLK-1, Notch-1) →→→

㈠ Common lymphoid progenitor(淋系祖细胞)（CD10,CD34,CD38）→Lymphoblast（原始淋巴细胞，成淋巴细胞，淋巴母细胞）→ Prolymphocyte (幼稚淋巴细胞，前淋巴细胞→Natural killer cell 自然杀伤细胞)→ Small lymphocyte （小淋巴细胞）→→

① B lymphocyte (B 淋巴细胞)→ Mature B-cell （成熟B细胞）：包括Memory B-cell；IgM secreting B-cell（分泌IgM）；Switched plasma cell (转换浆细胞→ 分泌IgA, IgD, IgE, IgG)

② T lymphocyte (T 淋巴细胞) →Tc cell (CD8⁺,TCRα/β → T-memory cell)；Th cell (CD4⁺,TCRα/β→ Th1，Th2，Th9，Th17.Th22，Treg调节性T细胞，T-memory cell)

㈡ Common myeloid progenitor(髓系祖细胞) （CD34,CD38,CD123,CD45RA^-）→→

① Granulocyte-monocyte progenitor(GMP粒-单祖细胞)（CD34,CD38,CD123,CD45RA）→ Myeloblast(原始粒细胞，成髓细胞)（CD13,CD15,CD33,CD91,CD114,CD116）→→

⑴ Neutrophilic promyelocyte(中性早幼粒细胞) → Neutrophilic myelocyte(中性中幼粒细胞) → Neutrophilic metamyelocyte(中性晚幼粒细胞) → Neutrophil (嗜中性粒细胞)[Neutrophilic band, neutrophilic stab form/cell, neutrophilic granulocyte band form（中性杆状核粒细胞）；Neutrophilic segmented granulocyte/cell, neutrophilic granulocyte segmented form,segmented neutrophil(中性分叶核粒细胞)]

⑵ Eosinophilic promyelocyte(嗜酸性早幼粒细胞) →Eosinophilic myelocyte(嗜酸性中幼粒细胞) →Eosinophilic metamyelocyte(嗜酸性晚幼粒细胞) → Eosinophil (嗜酸性粒细胞)[Eosinophilic band, eosinophilic stab form/cell, eosinophilic granulocyte band form（嗜酸性杆状核粒细胞）；Eosinophilic segmented granulocyte/cell, eosinophilic granulocyte segmented form,segmented eosinophil(嗜酸性分叶核粒细胞)]

⑶ Basophilic promyelocyte(嗜碱性早幼粒细胞) →Basophilic myelocyte(嗜碱性中幼粒细胞) →Basophilic metamyelocyte(嗜碱性晚幼粒细胞) → Basophil (嗜碱性粒细胞) [Basophilic band, basophilic stab form/cell, basophilic granulocyte band form（嗜碱性杆状核粒细胞）；Basophilic segmented granulocyte/cell, basophilic granulocyte segmented form,segmented basophil(嗜碱性分叶核粒细胞)]

⑷ Monoblast (原始单核细胞) →  Promonocyte（幼稚单核细胞）→  Monocyte（单核细胞 → Macrophage/Phagocyte 巨噬细胞；Myeloid dendritic cell 髓系树突状细胞)

② Megakaryocyte-erythroid progenitor (MEP 巨-红祖细胞)( CD34, CD38, CD123^-，CD45RA^-) →→

⑴ Promegakaryoblast(前原始巨核细胞) → Megakaryoblast (原始巨核细胞) → Promegakaryocyte（幼稚巨核细胞）→   megakaryocyte（巨核细胞）[Granular megakaryocyte颗粒型巨核细胞，Platelet-forming/producing megakaryocyte产板型巨核细胞，Nude nucleated megakaryocyte裸核型巨核细胞] → thrombocyte（platelet血小板，血栓细胞）

⑵ Proerythroblast (原始红细胞)(CD71, CD105, Glycophorin血型糖蛋白) → Basophilic erythroblast（早幼红细胞）→  Polychromatic erythroblast（中幼红细胞）→Orthochromatic erythroblast（晚幼红细胞）→ Polychromatic erythrocyte （嗜多色性红细胞）→  Erythrocyte（红细胞）

③ Mastoblast/Tissue mastoblast(原肥大细胞/原组织嗜碱细胞)→  Promastocyte/Tissue promastocyte (幼肥大细胞/幼组织嗜碱细胞)→ Mastocyte(Mast cell)/Tissue  basophil (肥大细胞/组织嗜碱细胞)

2. Primitive endoderm（原始内胚层）（CD325）→ Definitive endoderm (定形内胚层) (CD184) → Lung肺, Intestine肠, Pancreas胰腺, thyroid甲状腺, Liver肝脏, Thymus胸腺

Ⅱ：Ectoderm(外胚层) (NCAM,NOTCH1) →→→

⑴ Neural tube (神经管) (CD15, CD49f, CD57, CD81, CD95, CD146, CD184, CD271, CD288, CD349, ABCG2, Neuroglycan-C, Neuropilin-2, NOTCH1) → Motor neuron运动神经元,  Spinal cord脊髓, Neural pituitary神经垂体, Retina视网膜, Brain脑

⑵ Neural crest(神经嵴)(CD49d, CD57, CD271, NOTCH1) → dentine of teeth牙本质, Facial cartilage面部软骨, Adrenal medulla肾上腺髓质, Melanocyte黑色素细胞, Peripheral nervous system(周围神经系统) →(Schwann cell许旺细胞, Parasympathetic nervous system副交感神经系统, Neuroglia神经胶质, Sympathetic nervous system交感神经系统)

⑶ Outer ectoderm/Epidermis(外胚层) (CD71, p63) →  Lens and cornea晶状体和角膜, Epidermis(skin)表皮/上皮, Hair毛发, Nail指甲/趾甲, Sebaceous gland皮脂腺, Olfactory epithelium嗅觉上皮, Mouth epithelium 口腔上皮（→Anterior pituitary垂体前叶, Tooth enamel牙釉质/牙珐琅质, Cheek epithelium颊上皮）